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Cited by 362T-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model OrganismsPsoriasis: Treatment and Pathogenesis

Successful and Maladaptive T Cell Aging

Open access
Goronzy, Jörg J., Weyand, Cornelia M.·2017·Immunity
DOI 10.1016/j.immuni.2017.03.010PMC PMC5433436
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Abstract

Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation. We propose that immune failure occurs when adaptive strategies developed by the aging T cell system fail and also discuss how, in some settings, the programs associated with T cell aging culminates in a maladaptive response that directly contributes to chronic inflammatory disease.

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Crossref · 10.1016/j.immuni.2017.03.010

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 184 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Human T cell generation in adulthood depends on peripheral proliferation of naive T cells.

    “T cell generation during human adult life depends on peripheral proliferation of naive T cells”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites den Braber et al., 2012 source

      Not checked in the free run.

    • cites Sauce et al., 2012 source

      Not checked in the free run.

  • Interpretationreasoning

    Immune aging is a summation of adaptations that can be necessary and beneficial or harmful to the aging host.

    “Immune aging also is thus a summation of these adaptations, sometimes necessary and beneficial and sometimes harmful to the aging host.”
    Quote in the paperSubstantial claim
  • Interpretationnone given

    The T cell system adapts over life to changing resources and demands, producing a fundamentally restructured immune system in older people.

    “Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals.”
    Quote in the paperSubstantial claim
  • Premisecitation

    In later life, naive CD8+ T cells accelerate turnover.

    “Only in later life, naive CD8+ T cells accelerate their turnover”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Cicin-Sain et al., 2007 source

      Not checked in the free run.

    • cites Naylor et al., 2005 source

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    • cites Westera et al., 2015 source

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  • Interpretationnone given

    Homeostatic proliferation maintains T cell compartment size but causes partial loss of stemness and incomplete differentiation.

    “Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation”
    Quote in the paperSubstantial claim
  • May combine two claims. 84
  • Classified as probably not a substantial claim. 16
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Murine naive T cells survive about 30 days and divide from homeostatic proliferation only every 1-2 years.

    “Naive murine T cells survive for only 30 days, while cell divisions from homeostatic proliferation occur only every 1 to 2 years”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites den Braber et al., 2012 source

      Not checked in the free run.

    • cites Westera et al., 2013 source

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  • May combine two claims.

    Premisecitation

    Age-related functional changes in naive murine T cells are not caused by replication but by cellular longevity, which increases after thymectomy or in aged mice.

    “Age-associated functional changes in naive murine T cells are not a consequence of replication—they at most divide once throughout life—but are a corollary of cellular longevity that even increases after thymectomy or in aged mice”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bains et al., 2009a

      Not checked in the free run.

    • cites Tsukamoto et al., 2009 source

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  • May combine two claims.

    Interpretationnone given

    Negative regulatory programs activated during T cell aging limit effector T cell expansion and prevent increasing oligoclonality, but also interfere with memory cell generation.

    “the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Vaccination of older individuals is only partially successful; generating new immune memory and boosting existing memory are less efficient than in childhood.

    “Attempts to improve immune competence through vaccination programs of older individuals have been only partially successful; generating immune memory to new antigens and boosting existing memory are less efficient than in childhood”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gross et al., 1995 source

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    • cites Hainz et al., 2005 source

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    • cites Jefferson et al., 2005 source

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  • May combine two claims.

    Interpretationreasoning

    The murine naive T cell compartment depends entirely on thymic activity and shrinks as thymic activity declines.

    “the murine naive T cell compartment depends entirely on thymic activity and shrinks with its decline.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Waning adaptive immunity begins in mid adulthood, around age 50, and becomes clinically more relevant in the 7th-10th decades.

    “Evidence of waning adaptive immunity is already apparent in mid adulthood, as early as at the age of 50 years, with increasing clinical relevance in the 7th–10th decade of life”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Goronzy and Weyand, 2013 source

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    • cites Montecino-Rodriguez et al., 2013 source

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    • cites Pinti et al., 2016 source

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  • May combine two claims.

    Premisecitation

    In young adults the thymus contributes only 16% of total T cell generation, and in older individuals thymic contribution falls below 1%, so they rely almost entirely on peripheral proliferation.

    “Even in young adults, the thymus contributes only 16% of total T cell generation. Thymic contribution declines further to <1% in older individuals who therefore nearly exclusively rely on peripheral proliferation to repopulate T cells”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Bains et al., 2009a

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    • cites Nobile et al., 2004 source

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    • cites Westera et al., 2015 source

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  • May combine two claims.

    Premisecitation

    Daily turnover of naive CD4+ and CD8+ T cells remains stable at about 0.04% throughout adulthood, with no apparent compensatory increase in homeostatic proliferation with age.

    “Daily turnover rates of naive CD4+ and CD8+ T cells are stable throughout adulthood at about 0.04%, with no apparent need for compensatory increase in homeostatic proliferation with age.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Cicin-Sain et al., 2007 source

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    • cites Naylor et al., 2005 source

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    • cites Westera et al., 2015 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Compartmentalization of naive and memory CD4+ and CD8+ T cells in spleen, lymph nodes, and blood changes over life.

    “compartmentalization of naive and memory CD4+ and CD8+ T cells in spleen, lymph nodes, and blood changes over life”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Thome et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The distribution of TCR frequencies in an analyzed sample may not reflect the entire repertoire and likely changes with age, which hampers inferential estimates of overall richness.

    “The distribution of TCR frequencies in the analyzed sample does not necessarily reflect the distribution in the entire repertoire; moreover, the distribution is likely to change with age, hampering inferential estimates of overall richness”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Goronzy et al., 2015 source

      Not checked in the free run.

    • cites Laydon et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In human blood, naive-like Treg cells decrease and memory-like Treg cells increase with age.

    “with naive-like Treg cells decreasing and memory-like Treg cells increasing with age”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Seddiki et al., 2006 source

      Not checked in the free run.

    • cites Valmori et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This estimate is consistent with TREC frequencies and with modeling predicting that the number of distinct human TCR sequences is only one order of magnitude lower than the number of total naive cells.

    “This estimate is consistent with TREC frequencies as well as with modeling experiments which predict that the number of distinct sequences in humans is by only one order of magnitude lower than the number of total naive cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lythe et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mice have a smaller starting repertoire and functional holes have been described with age.

    “This is in contrast to mice, which have a smaller repertoire to start with and functional holes have been described with age”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yager et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent study found approximately equal loss of naive T cell subsets in spleen and selected lymphoid tissues, without preferential CD8+ loss.

    “a recent study found an approximately equal loss of naive T cell subsets in spleen and selected lymphoid tissues, without preference for CD8+ T cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Thome et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Reliable estimation of unique TCRs by next-generation sequencing is limited by excluding sequencing artifacts without excluding infrequent sequences and by extrapolating from small circulating samples to the large T cell pool.

    “The difficulties to reliably estimate the number of unique TCRs by next-generation sequencing derive from two major barriers: how can one exclude sequencing artifacts without excluding infrequent sequences, and how can one extrapolate from the analyses of small numbers of circulating cells to the large T cell pool if richness is much higher than the sample size?”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    All human T cell repertoire studies so far have been done in healthy older individuals, who are known to respond better to vaccination, and studies in frail individuals are lacking.

    “all human studies so far were done in healthy older individuals, known to respond better to vaccination. T cell repertoire studies in frail individuals are lacking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Absolute numbers of naive CD4+ T cells in peripheral blood are stable in the elderly, while circulating naive CD8+ T cells progressively decline with age.

    “Absolute numbers of naive CD4+ T cells in peripheral blood have been reported to be stable in the elderly. In contrast, circulating naive CD8+ T cells are progressively lost with age”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Czesnikiewicz-Guzik et al., 2008 source

      Not checked in the free run.

    • cites Wertheimer et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The number of divisions appears lower than needed to generate 10,000 descendants; TREC frequencies are more consistent with clonal sizes around 100 cells.

    “the number of divisions appears to be lower than what is required to generate 10,000 descendants. Frequencies of TCR excision circles (TRECs) that form during TCR-α rearrangement are more consistent with clonal sizes of around 100 cells”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Bains et al., 2009b

      Not checked in the free run.

    • cites den Braber et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S4 (based).

    Interpretationreasoning

    The prevailing view is that naive CD8+ T cells are less successfully maintained with age than naive CD4+ T cells.

    “the prevailing notion is that naive CD8+ T cells are less successfully maintained with age than naive CD4+ T cells”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Treg cells increase in skin and possibly other compartments, where they contribute to impaired T cell responses in older individuals.

    “Treg cells increase in the skin and possibly other compartments, where they contribute to impaired T cell responses in older individuals”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Vukmanovic-Stejic et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    T cell frequencies to VZV decline with age, likely exposing older individuals to VZV reactivation and shingles.

    “T cell frequencies to VZV decline with age, presumably exposing aging individuals to VZV reactivation, causing shingles”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Levin et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Most clonally expanded phenotypically naive T cells express TCR sequences that do not overlap with memory compartment sequences, so they probably represent truly naive cells that proliferated without exogenous antigen.

    “the majority of these clonally expanded, phenotypically naive T cells expressed TCR sequences that did not overlap with those expressed by T cells in the memory compartment and therefore probably represent truly naive cells that have proliferated without encountering exogenous antigens.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    T cell responses specific for latent herpes viruses are an informative model for understanding age-associated changes in T cell memory.

    “T cell responses specific for latent herpes viruses are an informative model to understand age-associated changes in T cell memory.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    An increasingly uneven clonal size distribution can be biologically relevant: some clones may be too infrequent to respond meaningfully, while expanded clones may respond more strongly to specific challenges.

    “Such an increasingly uneven clonal size distribution can be biologically relevant. Some clones may be just too infrequent in older individuals to provide a meaningful response to immune challenge, while expanded ones may confer increased responsiveness to specific challenges.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Memory T cell homeostasis is more dynamic than naive T cell homeostasis, with daily turnover around 0.6% and greater population heterogeneity in stable isotope-labeling studies.

    “memory T cell homeostasis is more dynamic than that of naive T cells with daily turnover rates of around 0.6%, shows evidence of a higher degree of population heterogeneity in stable isotope-labeling studies”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Wallace et al., 2004 source

      Not checked in the free run.

    • cites Westera et al., 2013 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Differences in CD4+ and CD8+ memory T cell persistence may contribute to discrepant CMV and VZV memory, because VZV is thought to be mainly controlled by CD4+ T cells, which may be less prone to memory inflation and differentiation than CD8+ TEMRAs.

    “Alternatively or in addition, dissimilarities in CD4+ and CD8+ T memory cell persistence may contribute because VZV is thought to be mainly controlled by CD4+ T cells which may be less prone to memory cell inflation and differentiation compared to CD8+ TEMRAs.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: VZV is mainly controlled by CD4+ T cells.

  • May combine two claims.

    Premisecitation

    The CD8+ compartment size is plastic and can accommodate expansion of CMV-specific cells.

    “the CD8+ compartment size is plastic and is capable of accommodating the expansion of CMV-specific cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites van Leeuwen et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Latent herpes virus infections (VZV, EBV, CMV) are very common and strongly influence peripheral blood T cell composition with age.

    “Latent infections with herpes viruses such as varicella zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) are very common in humans and have a major influence on the peripheral blood T cell composition with age.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Increased clonal sizes are a hallmark of immune memory, and clonal dominance is normal for memory T cell responses to a single peptide, likely due to antigen-driven selection.

    “Increase in clonal sizes is a hallmark of immune memory; moreover, clonal dominance is quite normal for the memory T cell repertoire responding to a single peptide”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Obar et al., 2008 source

      Not checked in the free run.

    • cites van Heijst et al., 2009 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    By age 80, almost 50% of individuals have experienced shingles.

    “By the age of 80 years, almost 50% of individuals have experienced shingles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Other studies found no relationship between CMV carrier status and reduced influenza vaccine responses with age; CMV infection even appeared to improve antibody responses in young individuals, possibly by activating innate cells.

    “other studies have not found a relationship between CMV carrier status and reduced influenza vaccine responses with age; on the contrary, CMV infection appeared to even have a positive effect on antibody responses in young individuals, presumably by activating innate cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Furman et al., 2015 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Mathematical modeling predicts that decay of resident memory T cells after infection and lag in generating new resident cells account for failed viral control in pulmonary influenza infection.

    “Mathematical modeling has predicted that their decay after infection and the lag-time in generating new resident cells accounts for failed viral control in pulmonary influenza infection”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Zarnitsyna et al., 2016 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    A possible explanation for divergent CMV findings is that CMV does not affect unrelated immune responses, but memory inflation needed to contain CMV is a surrogate marker of immune failure.

    “One possible explanation for these diverging observations is that CMV infection does not influence unrelated immune responses but that memory inflation, by itself necessary to contain CMV, is a surrogate marker of immune failure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Resident memory T cells seed tissues in childhood and persist throughout adulthood.

    “Seeding into tissues occurs in childhood, and the resident population persists throughout adulthood”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Farber et al., 2014 source

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    • cites Sathaliyawala et al., 2013 source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    CMV-specific effector T cells theoretically occupy a different tissue niche from naive or central memory cells and therefore should not constrain those cells' repertoire or vaccination responses.

    “Theoretically, CMV-specific effector T cells reside in a different tissue niche than naive or central memory cells and thus should not constrain the repertoire of these cells or their response to vaccination.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: CMV-specific effector T cells reside in a different tissue niche from naive or central memory cells.

  • May combine two claims.

    Premisenone given

    Current understanding of age effects on memory compartment size relies entirely on peripheral blood and lacks information on resident memory cells.

    “our current understanding of the influence of age on the size of the memory compartment entirely relies on studies of peripheral blood and lacks information on resident memory cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Memory cell inflation appears beneficial for controlling viral latency, and there is currently no convincing evidence that it has adverse effects on overall immunity.

    “Memory cell inflation appears to be beneficial for controlling viral latency while there is currently no convincing evidence that it has adverse effects on overall immunity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Discrepant T cell memory persistence to CMV and VZV could be due to differences in latency and viral load of these herpes virus strains.

    “Discrepant T cell memory persistence to CMV and VZV could be due to differences in latency and viral load of these herpes virus strains.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationreasoning

    Peripheral selection of proliferating cells could severely reduce compartment size and bias TCR diversity, and may correlate with larger loss in immune health.

    “Peripheral selection of proliferating cells could severely reduce compartment size and bias TCR diversity and may correlate with larger loss in immune health.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Circulating numbers, phenotypes, and costimulatory molecule expression of myeloid and plasmacytoid DCs appear intact in older individuals.

    “Circulating numbers of myeloid and plasmacytoid DCs, their phenotypes, and their ability to express costimulatory molecules appear to be intact in older individuals”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Agrawal et al., 2007 source

      Not checked in the free run.

    • cites Gupta, 2014 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Outside TEMRA populations, the overall number of TCR sequences does not decline with age and the number of clonally expanded memory T cells does not increase, suggesting overall diversity is well maintained.

    “Outside of the TEMRA populations, the overall number of TCR sequences does not decline with age and the number of clonally expanded memory T cells does not increase, suggesting that the overall diversity is well maintained”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Qi et al., 2014

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    T cell activation and differentiation require dendritic cells to present antigen, provide costimulatory signals, and supply lineage-determining cytokines, all sensitive to the inflammatory milieu.

    “To be activated and to differentiate, T cells require dendritic cells (DCs) to present antigen and provide costimulatory signals as well as lineage-determining cytokines, all processes that are sensitive to the inflammatory milieu.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Naive TCR sequence diversity in young adults is high and predicted to exceed functional diversity, so even a modest age-related loss is unlikely to have functional consequences.

    “The naive TCR sequence diversity in young adults is high and predicted to exceed the functional diversity so that even a modest loss with age is unlikely to have functional consequences.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Circulating levels of pro-inflammatory cytokines, especially IL-6 and TNF-α, increase with age and correlate with age-associated morbidities such as cardiovascular disease and frailty.

    “circulating levels of pro-inflammatory cytokines, in particular interleukin (IL)-6 and tumor necrosis factor (TNF)-α, increase with age, and these have been correlated with age-associated morbidities such as cardiovascular disease and frailty”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ferrucci et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Tonic signaling by inflammatory cytokines is expected to attenuate dendritic cell responsiveness to stimulation.

    “Tonic signaling by inflammatory cytokines is expected to attenuate the responsiveness of DCs to stimulation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Repertoire diversity of naive T cells in old individuals is important for primary T cell responses and remains a resource for responses to previously encountered antigens.

    “Repertoire diversity of naive T cells in old individuals is not only important for primary T cell response but continues to be a resource for T cell responses to antigens previously encountered.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Most studies describe reduced cytokine production by DCs stimulated with Toll-like receptor ligands in vitro, and this defect correlates with reduced vaccination responses.

    “Most studies describe reduced cytokine production of DCs stimulated with Toll-like receptor ligands in vitro, a defect that has been correlated with reduced responses to vaccination”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Panda et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    While memory inflation prevents overt clinical CMV disease in old adults, a smaller repertoire is related to more frequent asymptomatic CMV reactivations that may contribute to inflammation in older adults.

    “While memory inflation is sufficient to prevent overt clinical disease from CMV in old adults, a smaller repertoire has been related to more frequent CMV reactivations, which are clinically asymptomatic but may contribute to the inflammatory state in older adults.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Changes in the cytokine milieu or T cell responsiveness to cytokines could strongly influence maintenance of compartment size and repertoire diversity.

    “changes in the cytokine milieu or in the responsiveness of T cells to cytokine stimulation, as reviewed in the following section, could have a major influence on the ability to maintain compartment size and repertoire diversity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These conclusions depend on peripheral homeostatic proliferation being efficient and unbiased, which appears true for healthy older individuals but may not hold for all.

    “these conclusions are contingent on peripheral homeostatic proliferation being efficient and unbiased, which appears to be the case for healthy older individuals but may not hold up for all individuals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In comparative vaccination trials of older individuals, MF59 outperformed nonadjuvanted influenza vaccine in inducing virus-specific antibodies and improving clinical outcome.

    “In comparative vaccination trials of older individuals, MF59, widely used in Europe, outperformed the nonadjuvanted vaccine in inducing influenza virus-specific antibodies and improving clinical outcome”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Domnich et al., 2017 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Different cytokine milieus could bias functional polarization of T cell immunity.

    “Different cytokine milieus could bias the functional polarization of T cell immunity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    There is no convincing evidence that Th1 cell response induction is compromised in older individuals, consistent with DCs in the elderly producing IL-12 and a pro-inflammatory environment supporting Th1 responses.

    “There is no convincing evidence that the induction of a Th1 cell response is compromised in older individuals, consistent with the finding that DCs in the elderly can produce IL-12 and that a pro-inflammatory environment is supportive of Th1 cell responses.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    AS03-adjuvanted trivalent influenza vaccine showed a trend toward superior protection that reached significance for only some subtypes.

    “AS03-adjuvanted TIV vaccine showed a trend toward superior protection that, however, reached significance for only some subtypes”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites McElhaney et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Protein tyrosine kinase 7 and CD31 are expressed on a subpopulation of naive cells in children and young adults, are lost with homeostatic proliferation, and decline with age.

    “The cell surface molecules protein tyrosine kinase 7 and CD31, expressed on a subpopulation of naive cells in children and young adults, are lost with homeostatic proliferation and decline with age”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Haines et al., 2009 source

      Not checked in the free run.

    • cites Kilpatrick et al., 2008 source

      Not checked in the free run.

    • cites Kimmig et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Separate analysis of CD28+ and CD28− CD8+ T cells in young and old individuals was consistent with old CD28+CD8+ T cells being more differentiated, as also suggested by epigenetic studies.

    “A separate analysis of CD28+ and CD28− CD8+ T cells in young and old individuals were consistent with the model that old CD28+CD8+ T cells were more differentiated (Lazuardi et al., 2009) as also suggested by the epigenetic studies of CD8+ T cell subsets (Moskowitz et al., 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Lazuardi et al., 2009 source

      Not checked in the free run.

    • cites Moskowitz et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies of human T cells have associated aging with changes in autophagy, membrane raft properties, and reactive oxygen production, but these examined total T cell populations irrespective of naive or memory phenotype and are difficult to interpret.

    “Studies of human T cells have associated aging with changes in autophagy, in membrane properties to form rafts, and in reactive oxygen production (Fulop et al., 2014; Phadwal et al., 2012); however, these studies examined total T cell populations, irrespective of naive or memory phenotypes, and are therefore difficult to interpret.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Fulop et al., 2014 source

      Not checked in the free run.

    • cites Phadwal et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Expression of miR181a is highest in thymocytes, lower in naive T cells, and further declines with T cell differentiation in both mouse and men.

    “Expression of miR181a is highest in thymocytes, lower in naive T cells, and further declines with T cell differentiation in both mouse and men”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Li et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Activated CD4+ T cells from older individuals are less responsive to type I IFNs, mostly due to increased SHP1 recruitment to the IFAR signaling complex, potentially amplifying the effect of lower cytokine production.

    “activated CD4+ T cells from older individuals are also less responsive to type I IFNs, mostly due to increased recruitment of SHP1 to the IFAR signaling complex, potentially amplifying the effect from the lower production of this cytokine”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Le Page et al., 2014 source

      Not checked in the free run.

    • cites Li et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Frail individuals with higher inflammatory cytokine concentrations have reduced in vitro responses to cytokine stimulation and poorer vaccine responses in vivo, consistent with chronic cytokine exposure being harmful, possibly by attenuating signaling pathways.

    “Frail individuals who have higher concentrations of inflammatory cytokines also have reduced in vitro responses to cytokine stimulation and poorer vaccine responses in vivo, consistent with the model that chronic cytokine exposure is harmful, possibly by attenuating relevant signaling pathways.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In contrast to mouse virtual memory T cells, the age-related shift to a more differentiated state in human CD8+ T cells was incomplete and not associated with a gain in effector function, but included genes relevant to T cell proliferation.

    “In contrast to virtual memory T cells in the mouse, this shift to a more differentiated state was incomplete and not associated with a gain in effector function, but included genes relevant to T cell proliferation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Moskowitz et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The pro-inflammatory environment may cause blunted T cell responses to cytokines in older individuals, possibly through induction of negative regulatory pathways.

    “the pro-inflammatory environment may be responsible for the blunted response of T cells from older individuals to cytokines, as shown by in vitro studies, possibly due to the induction of negative regulatory pathways”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shen-Orr et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Monocytes in older individuals produce more IL-10 after influenza vaccination, which inversely correlates with antibody titer increase.

    “monocytes in older individuals produce more IL-10 after influenza vaccination, which inversely correlated with the increase in antibody titers”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mohanty et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    An analysis of age influence on the transcriptome in total CD4+ T cells identified relatively few gene expression differences with no striking pathway enrichment.

    “An analysis of the influence of age on the transcriptome in total CD4+ T cells identified relatively few gene expression differences with no striking pathway enrichment”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Reynolds et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These adjuvants appear efficacious in older individuals but cannot fully restore adaptive immune responses to the level of younger adults, possibly except for the VZV vaccine.

    “These adjuvants therefore appear to be efficacious in older individuals, but they cannot fully restore the adaptive immune response to the level of younger adults, possibly with the exception of the VZV vaccine.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Baseline STAT phosphorylation is increased in cells from older individuals, and reduced JAK-STAT signaling to cytokines correlates with chronic inflammation and age-associated morbidities.

    “Baseline STAT phosphorylation is increased in cells from older individuals, and reduced JAK-STAT signaling to cytokines have been correlated with chronic inflammation and age-associated morbidities.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The shift toward differentiation may result from cumulative replicative history of homeostatic proliferation over lifetime.

    “This shift may be a consequence of the cumulative replicative history of homeostatic proliferation over lifetime”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    After vaccination, T follicular helper cells are less frequent in older subjects and appear to malfunction.

    “after vaccination, T follicular helper (Tfh) cells are less frequent in older subjects and appear to be malfunctioning”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Barnett et al., 2014 source

      Not checked in the free run.

    • cites Herati et al., 2014 source

      Not checked in the free run.

    • cites Linterman, 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PD-1 expression is low and T-bet expression is high in TEMRAs.

    “PD-1 expression is low and T-bet expression is high in TEMRAs”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Henson et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In older individuals, clonal expansion of Mart1-specific T cells was reduced, and these cells failed to differentiate into T-bet-expressing effector T cells.

    “In older individuals, clonal expansion of Mart1-specific T cells was reduced, and importantly, these cells failed to differentiate into T-bet-expressing effector T cells.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Briceño et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    miR181a targets several phosphatases, including DUSP6, which is overexpressed in older T cells.

    “miR181a targets several phosphatases, including the dual-specific phosphatase (DUSP)6 that is overexpressed in older T cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Li et al., 2012

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    TEMRA T cells have low proliferative potential, short telomeres, and low telomerase activity and are considered senescent.

    “TEMRA T cells have low proliferative potential, short telomeres, and low telomerase activity and are considered to be senescent.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Activation of the p38 pathway is directly involved in loss of telomerase activity and proliferative capacity, as well as increased production of inflammatory cytokines similar to the senescence-associated secretory phenotype in fibroblasts.

    “Activation of the p38 pathway is directly involved in the loss of telomerase activity and of proliferative capacity, as well as the increased production of inflammatory cytokines similar to the senescence-associated secretory phenotype in fibroblasts”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tchkonia et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TEMRAs are different from exhausted cells because they have a selective defect in cell cycle progression, including a defect in telomerase expression, but are otherwise functionally competent.

    “TEMRAs are different from exhausted cells because they have a selective defect in cell cycle progression, including a defect in telomerase expression, but are otherwise functionally competent”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Akbar and Henson, 2011

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TEMRAs develop features of NK cells, leading to the interpretation that adaptive and innate immunity converge with age.

    “They develop features of NK cells leading to the interpretation that adaptive and innate immunity converge with age”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Pereira and Akbar, 2016

      Not checked in the free run.

    • cites Warrington et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These data assign a role to purinergic signaling in recall responses and point to a more prominent role for this pathway in older individuals.

    “These data assign a role to purinergic signaling in recall responses and also point to a more prominent role for this pathway in older individuals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The incidence of clinical disease due to reactivations of CMV and EBV is very low in elderly individuals, in contrast to severely immunosuppressed transplant patients.

    “Support for the functionality of these cells also comes from the observation that the incidence of clinical disease due to reactivations of CMV and EBV is very low in elderly individuals, in contrast to severely immunosuppressed transplant patients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rowshani et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Vaccine studies can be better controlled than population studies, and the evidence for impaired CD8+ T cell priming by age is overall convincing.

    “However, vaccine studies can be better controlled than population studies, and the evidence for impaired CD8+ T cell priming by age is overall convincing.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Proliferative responses of influenza M1-specific CD8+ T cells after TIV vaccination inversely correlated with telomere length in peripheral blood mononuclear cells, consistent with cumulative homeostatic proliferation constraining expansion of antigen-specific CD8+ T cells.

    “The proliferative responses of influenza M1-specific CD8+ T cells after TIV vaccination inversely correlated to telomere length in peripheral blood mononuclear cells (Najarro et al., 2015), consistent with the notion that cumulative homeostatic proliferation constrains the expansion of antigen-specific CD8+ T cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Najarro et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TEMRA T cells are mostly specific for latent viruses such as CMV and EBV, suggesting that nature and chronicity of viral stimulation rather than age drives their functional phenotype.

    “As discussed above, these cells are mostly specific for latent viruses, such as CMV and EBV (Newell et al., 2012), suggesting that the nature and chronicity of viral stimulation rather than age drives their functional phenotype”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Newell et al., 2012 source

      Not checked in the free run.

    • cites Wertheimer et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DUSP6 dephosphorylates ERK, attenuating ERK signaling after TCR activation and interfering with a forward feedback loop in TCR signaling.

    “DUSP6 dephosphorylates ERK, not only attenuating ERK signaling after TCR activation but also interfering with a forward feedback loop in TCR signaling”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Stefanová et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Naive CD8+ T cells appear more vulnerable to cell-intrinsic defects than CD4+ T cells, matching their higher degree of decline in peripheral blood with age.

    “Naive CD8+ T cells appear to be more vulnerable to developing cell-intrinsic defects than CD4+ T cells, matching their higher degree of decline in peripheral blood with age.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Interpretationreasoning

    Loss in NRF1 binding appears to account for reduced expression of mitochondrial respiratory chain genes and defective oxidative phosphorylation that could result in poor T cell survival, reminiscent of mitochondrial dysfunction-associated senescence.

    “The loss in NRF1 binding appears to account for the reduced expression of mitochondrial respiratory chain genes and defective oxidative phosphorylation that could result in poor T cell survival”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wiley et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In healthy aging, humans utilize this mechanism of cell generation successfully, particularly for CD4+ T cells, yet pay the price of imposing replicative stress on somatic cells that limits replicative potential and triggers cell differentiation.

    “In healthy aging, humans utilize this mechanism of cell generation quite successfully, in particular for CD4+ T cells, yet pay the price of imposing replicative stress on somatic cells that inherently limits their replicative potential and also triggers cell differentiation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Proliferation of TEMRAs is in part restored by PD-1 blockade, yet without improving telomerase activity.

    “Proliferation of TEMRAs is in part restored by PD-1 blockade, yet without improving telomerase activity”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Henson et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a meta-analysis of randomized controlled trials of immune checkpoint inhibitors, response rates of young and old cancer patients were very similar, suggesting that aging does not influence the function of exhausted T cells.

    “In a meta-analysis of randomized controlled trials of immune checkpoint inhibitors (ipilimumab, tremelimumab, nivolumab, and pembrolizumab), the response rates of young and old cancer patients were very similar, suggesting that aging does not influence the function of exhausted T cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Nishijima et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    This decline is significantly accelerated in RA T cells and affects the naive CD4+ compartment much more than the memory compartment.

    “This process is significantly accelerated in RA T cells and affects the naive CD4+ compartment much more than the memory compartment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Repression of PGC1α, an important cofactor of NRF1 activity, is an early event in T cell exhaustion, indicating a mechanistic overlap between T cell aging and exhaustion.

    “Repression of PGC1α, an important cofactor of NRF1 activity, is an early event in T cell exhaustion, indicating a mechanistic overlap between T cell aging and exhaustion”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bengsch et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    T cells rendered MRE11A-deficient infiltrate into synovial tissue where they promote a strong inflammatory response, inducing the hallmark RA cytokine signature of excessive IL-6, IL-1β, and TNF-α production.

    “T cells rendered MRE11A-deficient infiltrate into synovial tissue where they promote a strong inflammatory response, inducing the hallmark RA cytokine signature of excessive IL-6, IL-1β, and TNF-α production.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    CD8+CD45RO+CCR7− effector memory T cells from older individuals show only few differences in chromatin accessibility compared to young effector memory T cells, and they lack epigenetic signatures of exhausted T cells.

    “However, CD8+CD45RO+CCR7− effector memory T cells from older individuals show only few differences in terms of chromatin accessibility compared to young effector memory T cells, and they lack the epigenetic signatures of exhausted T cells”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Moskowitz et al., 2017 source

      Not checked in the free run.

    • cites Sen et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    This observation suggests that T cell aging mainly affects naive and central memory CD8+ T cells, possibly employing pathways similar to exhaustion.

    “This observation suggests that T cell aging mainly affects naive and central memory CD8+ T cells, possible employing pathways similar to exhaustion.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The aging memory T cell system has to find a balance between maintaining and expanding memory cells while avoiding oligoclonality and clonal dominance.

    “Generally, the aging memory T cell system has to find a balance between maintaining and expanding memory cells, while avoiding oligoclonality and clonal dominance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    MRE11Alo telomeres in RA T cells are coated by damage proteins and resemble uncapped, structurally abnormal telomeres.

    “MRE11Alo telomeres in RA T cells are coated by damage proteins and resemble uncapped, structurally abnormal telomeres.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Impairment of the nuclease induces senescence markers p16 and p21 but fails to upregulate p53, avoiding the classical hallmark of senescence, irreversible cell cycle arrest.

    “Impairment of the nuclease induces the senescence markers p16 and p21 but fails to upregulate p53, thus avoiding the classical hallmark of senescence, irreversible cell cycle arrest.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Understanding mechanisms driving healthy and maladaptive T cell aging is beginning to provide molecular targets and opens the door toward therapeutic corrections, extending life and functionality of T cells and preventing aging-related inflammation.

    “Understanding mechanisms driving healthy and maladaptive T cell aging is beginning to provide a series of molecular targets and opens the door toward therapeutic corrections, extending the life and functionality of T cells and preventing aging-related inflammation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    With maintained proliferative capacity, MRE11A RA T cells become highly mobile and capable of effective pro-inflammatory functions in the tissue environment.

    “With maintaining proliferative capacity, MRE11A RA T cells become highly mobile, capable of effective pro-inflammatory functions in the tissue environment”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Immune failure occurs when adaptive strategies developed by the aging T cell system fail.

    “As outlined in previous sections, immune failure occurs when adaptive strategies developed by the aging T cell system fail.”
    Quote in the paperSubstantial claim
97 of 97

  • The authors state this as an assumption.

    The naive T cell compartment is not biased by antigen stimulation, and peripheral blood can represent the overall naive T cell population.

    “Assuming that the naive T cell compartment is not biased by antigen stimulation and taking into account the conduit function of circulating blood, the peripheral blood compartment may be considered representative of the overall naive T cell population.”

  • The paper relies on this without support.

    The challenges that drive T cell adaptations differ substantially between rodents and humans, making translation uncertain.

    “Since challenges that drive these adaptations are quite different for rodents, it is uncertain whether and which insights from rodent aging can be translated to human physiology.”

  • The paper relies on this without support.

    VZV is mainly controlled by CD4+ T cells.

    “VZV is thought to be mainly controlled by CD4+ T cells”

  • The authors state this as an assumption.

    CMV-specific effector T cells reside in a different tissue niche from naive or central memory cells.

    “Theoretically, CMV-specific effector T cells reside in a different tissue niche than naive or central memory cells”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Telomere correlation points opposite to the stated interpretation

    Minor

    An inverse correlation means greater proliferation is associated with shorter telomeres. That points opposite to the stated interpretation that accumulated proliferation constrains subsequent expansion.

1 of 1

The citation lists haven’t been fetched yet

References 164 · Cited by 362

Research works printed but not linked: 2

  1. Gross, 1995, The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature, Ann. Intern. Med., 123, 518, 10.7326/0003-4819-123-7-199510010-00008 · DOI · Paper page
  2. Phadwal, 2012, A novel method for autophagy detection in primary cells: impaired levels of macroautophagy in immunosenescent T cells, Autophagy, 8, 677, 10.4161/auto.18935 · DOI · Paper page

Authors
Goronzy, J. J., & Weyand, C. M.
Affiliations
VA Palo Alto Health Care System (US)
Corresponding author
  • Goronzy, Jörg J.
  • Weyand, Cornelia M.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2017-03
Volume
46
Issue
3
Pages
364-378
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2017.03.010
PMC
PMC5433436
OpenAlex
W2602237780
Semantic Scholar
ed7fffb44ba823f357cf0c1d7c45d3d910755d45
Cited by
362
References
164
Citations by year
2026: 26 · 2025: 32 · 2024: 54 · 2023: 41 · 2022: 40 · 2021: 54 · 2020: 49 · 2019: 29 · 2018: 30 · 2017: 7
FWCI
3.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (I01 BX001669, P01 HL129941, R01 AI108891, R01 AR042527, R01 HL117913, R01 AG045779, R01 AI108906, U19 AI057266)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
T cell senescence, immunosenescence, homeostatic proliferation, T cell stemness, oligoclonality, memory T cells, immune failure, chronic inflammation
MeSH terms
Animals, Humans, T-Lymphocytes, Cellular Senescence

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Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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