Cited by 1,830T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells

Kaech, Susan M, Tan, Joyce T, Wherry, E John, Konieczny, Bogumila T, Surh, Charles D, Ahmed, Rafi·2003·Nature Immunology

DOI 10.1038/ni1009

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Abstract

A major unanswered question is what distinguishes the majority of activated CD8 T cells that die after an acute viral infection from the small fraction (5-10%) that survive to become long-lived memory cells. In this study we show that increased expression of the interleukin 7 receptor alpha-chain (IL-7Ralpha) identifies the effector CD8 T cells that will differentiate into memory cells. IL-7R(hi) effector cells contained increased amounts of antiapoptotic molecules, and adoptive transfer of IL-7R(hi) and IL-7R(lo) effector cells showed that IL-7R(hi) cells preferentially gave rise to memory cells that could persist and confer protective immunity. Thus, selective expression of IL-7R identifies memory cell precursors, and this marker may be useful in predicting the number of memory T cells generated after infection or immunization.

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“CD127 is constitutively expressed by naı̈ve cells, downregulated on the majority of antigen-specific CD8 T cells during T-cell activation, and expressed on memory CD8 T cells (21, 23).”
Background
Identification of Murine Poxvirus-Specific CD8+ CTL Epitopes with Distinct Functional Profiles
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“It is tempting to speculate that varying levels of IL-7R on these two distinct VV-specific T cells may explain why responses to peptide MVA-029 are stable and long-lasting, whereas responses to peptide MVA-043 are short-lived (14).”
Background
Tracking Antigen-Specific CD8 T Lymphocytes in the Lungs of Mice Vaccinated with the Mtb72F Polyprotein
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“We first measured CD127 (IL-7 receptor) expression, as IL-7 is critical for memory T cell homeostasis, and high CD127 expression is associated with long-lived memory CD8+ cells, while low CD127 expression can indicate chronic activation and exhaustion (30, 31).”
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Background
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Background
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Background
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Background
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Background
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BackgroundSelf-citation
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Method
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Background
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Self-citation
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Result
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BackgroundInfluential
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Background
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“The expression of IL-7R on effector CD8 T cells predicts the further differentiation into memory cells (1, 3, 4).”
Background
Culling of Activated CD4 T Cells during Typhoid Is Driven by Salmonella Virulence Genes
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“1, CD127, programmed cell death-1 (PD-1), PD-1 ligand (PD-L1), PD-2 ligand (PD-L2), CTLA-4, and isotype control Abs were purchased from eBioscience and BD Biosciences.”
BackgroundInfluential
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Self-citation
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“survival of IL-7Ra–expressing T cells that continue to differentiate into a relatively stable memory population with a heightened capacity for recall (3, 4).”
BackgroundSelf-citation
A Higher Activation Threshold of Memory CD8+ T Cells Has a Fitness Cost That Is Modified by TCR Affinity during Tuberculosis
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Briceño, P., Rivas-Yáñez, E., Rosemblatt, M. V., Parra-Tello, B., Farías, P., Vargas, L., Simon, V., Cárdenas, C., Lladser, Á., Salazar‐Onfray, F., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.638037 · Cited by 49
“distinguished following CD8+ T cell activation and clonal expansion: short-lived effector cells and memory effector cells (Kaech et al., 2003; Badovinac et al., 2004; Joshi et al., 2007).”
Background
The Role of CD4+ Resident Memory T Cells in Local Immunity in the Mucosal Tissue – Protection Versus Pathology –
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Protective CD8 T Cell Memory Is Impaired during Chronic CD70-Driven Costimulation
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BackgroundInfluential
Differential Regulation of Granzyme and Perforin in Effector and Memory T Cells following Smallpox Immunization
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“Recently, it was proposed that the IL-7R chain (CD127) might distinguish effector cells that survive the contraction phase and develop into functional memory cells (37).”
Background
Duration of Antigen Expression In Vivo following DNA Immunization Modifies the Magnitude, Contraction, and Secondary Responses of CD8+ T Lymphocytes
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The peripheral blood transcriptome reflects variations in immunity traits in swine: towards the identification of biomarkers
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Background
Cellular and molecular mechanisms of memory T-cell survival
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“In addition, they show enhanced ability of Ag-independent self-renewal [14,15], through homeostatic turnover in response to cytokines such as IL-2, IL-7, IL-15, and IL-21 [16–22], rapid clonal proliferation and functional activation upon re-encountering the same pathogen [23,24].”
Background
A context-dependent role for IL-21 in modulating the differentiation, distribution, and abundance of effector and memory CD8 T cell subsets
Tian, Y., Cox, M., Kahan, S. M., Ingram, J. T., Bakshi, R. K., & Zajac, A. (2016) · Journal of Immunology · doi:10.4049/jimmunol.1401236 · Cited by 45
“IL-7 and IL-15 are key regulators of T cell homeostasis, with IL-7 operating to promote survival and IL-15, mainly supporting basal homeostatic proliferation (38, 48, 59, 60).”
Background
Listeria Monocytogenes: A Model Pathogen Continues to Refine Our Knowledge of the CD8 T Cell Response
Qiu, Z., Khairallah, C. F., & Sheridan, B. S. (2018) · Pathogens · doi:10.3390/pathogens7020055 · Cited by 53
“While both SLEC and MPEC express TGF-β receptor, IL-7 but not IL-15 seems to be able to overcome the apoptotic effect induced by TGF-β.”
BackgroundInfluential
Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates
Chng, M. H. Y., Lim, M. Q., Rouers, A., Becht, É., Lee, B. T. K., MacAry, P. A., Lye, D. C., Leo, Y., Chen, J., Fink, K., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.10.007 · Cited by 45
IL‐7 derived from lymph node fibroblastic reticular cells is dispensable for naive T cell homeostasis but crucial for central memory T cell survival
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CD8+ Cytotoxic T-APC Stimulate Central Memory CD8+ T Cell Responses via Acquired Peptide-MHC Class I Complexes and CD80 Costimulation, and IL-2 Secretion
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“4C), indicating they may be central memory CD8 T (cmCTL) cells (CD44 CD62LIL-7R ) (25, 26).”
Background
Suppressor of Cytokine Signaling 1 Stringently Regulates Distinct Functions of IL-7 and IL-15 In Vivo during T Lymphocyte Development and Homeostasis
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“It was recently shown that a small population of CD127 CD8 T cells detected early after lymphocytic choriomeningitis virus infection, both among total and activated antigen-specific CD8 T cells, defined a population of precursors of memory CD8 T cells (19).”
BackgroundInfluential
Making memories that last a lifetime: heritable functions of self-renewing memory CD8 T cells
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Self-citation
Effector and memory CD8+ T cells as seen in immunity to malaria
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“studies showing that IL-15, IL-7, and IL-2 are critical for the development of memory CD8þ cells (90, 91), indicate the existence of several cytokine-mediated mechanisms that affect”
Background
Development and Function of Protective and Pathologic Memory CD4 T Cells
Jaigirdar, S. A., & MacLeod, M. K. L. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00456 · Cited by 49
“In CD8 T cells, recently activated T cells that express high levels of CD127 are more prone to develop into memory cells (78).”
Background
Decreases in IL-7 levels during antiretroviral treatment of HIV infection suggest a primary mechanism of receptor-mediated clearance
Hodge, J. N., Srinivasula, S., Hu, Z., Read, S. W., Porter, B. O., Kim, I., Mican, J. M., Paik, C. H., DeGrange, P., Mascio, M. D., et al. (2011) · Blood · doi:10.1182/blood-2010-12-323600 · Cited by 46
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“As expected (19), ICAM-1 CD127, KLRG-1 CD8 T cells expanded upon secondary challenge, whereas the recall response of the ICAM-1 CD127, KLRG-1 memory cells was significantly lower (Fig.”
Background
CD4+ T helper cells use CD154–CD40 interactions to counteract T reg cell–mediated suppression of CD8+ T cell responses to influenza
Ballesteros‐Tato, A., León, B., Lund, F. E., & Randall, T. D. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20130097 · Cited by 46
“…through the transmembrane domain of the TCR (Teixeiro et al., 2009), and signals from cytokines such as IL-2 (Williams et al., 2006; Feau et al., 2011), IL-7 (Kaech et al., 2003; Ma et al., 2006), and IL-15 (McGill et al., 2010) are required during the contraction phase of the immune response.”
BackgroundInfluential
CD27 Stimulation Promotes the Frequency of IL-7 Receptor-Expressing Memory Precursors and Prevents IL-12–Mediated Loss of CD8+ T Cell Memory in the Absence of CD4+ T Cell Help
Dong, H., Franklin, N. A., Roberts, D. J., Yagita∥, H., Glennie, M. J., & Bullock, T. N. J. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103329 · Cited by 46
“From the pool of CD8 T cells that expand in response to immunization, those with a greater capacity for survival (termed memory precursor effector cells [MPECs]) are enriched within a population of cells that re-express the IL-7R (5, 6), whereas terminally differentiated effector cells with little capacity to survive…”
Background
Expression of IL‐7Rα and KLRG1 defines functionally distinct CD8 + T‐cell populations in humans
Remmerswaal, E. B. M., Hombrink, P., Nota, B., Pircher, H., ten Berge, I. J. M., van Lier, R. A. W., & van Aalderen, M. C. (2019) · European Journal of Immunology · doi:10.1002/eji.201847897 · Cited by 44
Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway
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Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus
Shinzawa, M., Moseman, E. A., Gossa, S., Mano, Y. M., Bhattacharya, A., Guinter, T. I., Alag, A., Chen, X., Cam, M. C., McGavern, D. B., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01187-1 · Cited by 45
Interleukin-7 Receptor Expression on CD8 T-Cells Is Downregulated by the HIV Tat Protein
Faller, E., McVey, M. J., Kakal, J. A., & MacPherson, P. A. (2006) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/01.qai.0000230319.78288.f4 · Cited by 46
Cutting Edge: Limiting Amounts of IL-7 Do Not Control Contraction of CD4+ T Cell Responses
Tripathi, P., Mitchell, T. C., Finkelman, F. D., & Hildeman, D. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4027 · Cited by 46
“Thus, the proportion of 2W1S-specific T cells that are CD127 increased during the contraction phase of the response, as has been previously described in other models (1, 2, 8).”
BackgroundResult
Friends Not Foes: CTLA-4 Blockade and mTOR Inhibition Cooperate during CD8+ T Cell Priming To Promote Memory Formation and Metabolic Readiness
Pedicord, V. A., Cross, J. R., Montalvo-Ortiz, W., Miller, M. L., & Allison, J. P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402390 · Cited by 45
“This phenotype has been described to be associated with memory precursor CD8 T cells (4, 20) and recapitulates memory precursor increases previously seen with low doses of”
Background
Cancer vaccines for established cancer: how to make them better?
Andrews, D. M., Maraskovsky, E., & Smyth, M. J. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00612.x · Cited by 46
“CD8(1) T-cell memory is controlled by IL-7, and only cells expressing IL-7Ra (CD127) are capable of surviving long term (68), giving rise to subpopulations of antigen-specific cells termed effector and central memory cells.”
Background
microRNAs function in CD8+T cell biology
Liang, Y., Pan, H., & Ye, D. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.1ru0814-369r · Cited by 45
“least 2 subsets: SLECs, which have poor longevity, exhibit a terminally differentiated phenotype, and lack the ability for antigen-independent homeostatic proliferation, and MPECs, which efficiently survive the contraction phase, acquire memory properties, and constitute the majority population of cells in the memory…”
mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA
Diken, M., Kreiter, S., Vascotto, F., Selmi, A., Attig, S., Diekmann, J., Huber, C., Türeci, Ö., & Sahin, U. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0046 · Cited by 45
“1C), which is known to contribute to the overall cellular fitness and survival of CD8þ T cells (15).”
Background
Latent Virus Influences the Generation and Maintenance of CD8+ T Cell Memory
Sheridan, B. S., Khanna, K. M., Frank, G. M., & Hendricks, R. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8356 · Cited by 45
“Within lymphoid organs, the size of the memory precursor pool is proportional to the size of the effector pool (8).”
BackgroundInfluential
Combination of an autophagy inhibitor with immunoadjuvants and an anti-PD-L1 antibody in multifunctional nanoparticles for enhanced breast cancer immunotherapy
Cheng, Y., Wang, C., Wang, H., Zhang, Z., Yang, X., Dong, Y., Ma, L., & Luo, J. (2022) · BMC Medicine · doi:10.1186/s12916-022-02614-8 · Cited by 45
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Insights into phenotypic and functional CD8 + TRM heterogeneity
Heeg, M., & Goldrath, A. W. (2023) · Immunological Reviews · doi:10.1111/imr.13218 · Cited by 45
Two Kinetic Patterns of Epitope-Specific CD8 T-Cell Responses following Murine Gammaherpesvirus 68 Infection
Freeman, M. L., Lanzer, K. G., Cookenham, T. S., Peters, B., Sidney, J., Wu, T.-T., Sun, R., Woodland, D. L., Sette, A., & Blackman, M. A. (2010) · Journal of Virology · doi:10.1128/jvi.02229-09 · Cited by 44
“We also examined the memory phenotype by examining surface expression of CD127 (interleukin-7R [IL-7R ]), a marker that is expressed on naive cells, is downregulated during activation, and is reexpressed during memory (19, 29), and KLRG-1, a marker of terminal differentiation (Fig.”
Background
Regulation of memory T cells by γc cytokines
Osborne, L. C., & Abraham, N. B. (2009) · Cytokine · doi:10.1016/j.cyto.2009.09.008 · Cited by 47
“the peak of the primary T cell response [58].”
Background
Both HLA-B*57 and Plasma HIV RNA Levels Contribute to the HIV-Specific CD8 + T Cell Response in HIV Controllers
Lécuroux, C., Sáez‐Cirión, A., Girault, I., Versmisse, P., Boufassa, F., Avettand-Fènoël, V., Rouzioux, C., Meyer, L., Pancino, G., Lambotte, O., et al. (2013) · Journal of Virology · doi:10.1128/jvi.02098-13 · Cited by 44
“Cells expressing CD127, the IL-7-R chain, are known as memory cells with high proliferating capacities (28, 29).”
Background
THE IMPACT OF TCR SIGNAL STRENGTH ON RESIDENT MEMORY T CELL FORMATION DURING INFLUENZA VIRUS INFECTION
Fiege, J. K., Stone, I. A., Fay, E. J., Markman, M., Wijeyesinghe, S. P., Macchietto, M., Shen, S. S., Masopust, D., & Langlois, R. (2019) · Journal of Immunology · doi:10.4049/jimmunol.1900093 · Cited by 43
“Memory CD8 T cell differentiation is shaped by the strength of TCR stimulation in which higher affinity interaction correlates with greater TEM generation over TCM generation (17), elevated KLRG1 expression, reduced CD127 (IL-7Ra) expression (33, 34), 938 LOW-AFFINITY TCR STIMULATION FAVORS TRM ESTABLISHMENT”
Background
Hepatitis B virus-triggered PTEN/β-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion
Sun, Y., Yu, M., Qu, M., Ma, Y., Zheng, D., Yue, Y., Guo, S., Tang, L., Li, G., Zheng, W., et al. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00197.2019 · Cited by 44
Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma
Hsu, P., Yang, T., Kao, J., Cheng, K.-S., Lee, Y.-J., Wang, Y.-M., Hsieh, C.-T., Lin, C., & Wu, Y. (2010) · Liver International · doi:10.1111/j.1478-3231.2010.02323.x · Cited by 44
“In addition, high levels of PD-1 and low levels of CD127 are linked to a functionally ‘exhausted’ phenotype of HCV-specific CD8(1) T cells in chronic infection (18).”
Background
Committed to memory: lineage choices for activated T cells
Moulton, V. R., & Färber, D. L. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.04.006 · Cited by 43
Early Decision: Effector and Effector Memory T Cell Differentiation in Chronic Infection
Opata, M. M., & Stephens, R. (2014) · Current Immunology Reviews · doi:10.2174/1573395509666131126231209 · Cited by 46
“CD127+ and CD127- populations, decay more slowly [22, 96, 120]”
Influential
Reduced numbers of IL‐7 receptor (CD127) expressing immune cells and IL‐7‐signaling defects in peripheral blood from patients with breast cancer
Vudattu, N. K., Magalhaes, I., Schmidt, M., Seyfert‐Margolis, V., & Maeurer, M. J. (2007) · International Journal of Cancer · doi:10.1002/ijc.22854 · Cited by 44
“%) in CD41 T-cells.”
BackgroundInfluential
Activation and Inactivation of Antiviral CD8 T Cell Responses during Murine Pneumovirus Infection
Claassen, E. A. W., van der Kant, P. A. A., Rychnavska, Z. S., van Bleek, G. M., Easton, A. J., & der Most, R. G. V. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6597 · Cited by 44
“7c), suggesting that these dysfunctional memory cells were maintained by IL-7 (36).”
BackgroundInfluential
Reversal of age-associated thymic atrophy: Treatments, delivery, and side effects
Aspinall, R., & Mitchell, W. A. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2008.04.014 · Cited by 44
PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients
Shen, T., Zheng, J., Xu, C., Liu, J., Zhang, W., Lu, F., & Zhuang, H. (2010) · Virology Journal · doi:10.1186/1743-422x-7-310 · Cited by 45
“As a subunit (a chain) of IL-7 receptor, CD127/IL-7 system plays an essential role in maintaining homeostasis of circulating T cells, including naïve and memory T cells under physiological as well as immune disordered conditions[27,28].”

Authors: Kaech, S. M., Tan, J. T., Wherry, E. J., Konieczny, B. T., Surh, C. D., & Ahmed, R.
Affiliations: Emory University (US)
Scripps Research Institute (US)
Corresponding author: Ahmed, Rafi
ORCID: Kaech, Susan M
Wherry, E John
Surh, Charles D
Ahmed, Rafi
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2003-11-16
Volume: 4
Issue: 12
Pages: 1191-1198
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1009
OpenAlex: W1974842026
Cited by: 1,830
References: 48
Citations by year: 2026: 41 · 2025: 57 · 2024: 42 · 2023: 63 · 2022: 67 · 2021: 69 · 2020: 67 · 2019: 70 · 2018: 56 · 2017: 59 · 2016: 77 · 2015: 73 · 2014: 73 · 2013: 96 · 2012: 91
FWCI: 30.27
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: CD127, CD8+ T cells, effector T cells, memory T cells, apoptosis, adoptive transfer, viral infection, protective immunity, memory T cell generation
MeSH terms: Animals, Antigens, Surface, Cell Differentiation, Immunologic Memory, Lymphocyte Activation, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Transgenic, Signal Transduction, Gene Expression, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Cell Lineage, Adoptive Transfer, Receptors, Interleukin-7, Oligonucleotide Array Sequence Analysis, Mice

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Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells

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