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

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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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Background
Priming CD8+ T cells with dendritic cells matured using TLR4 and TLR7/8 ligands together enhances generation of CD8+ T cells retaining CD28
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BackgroundInfluential
TLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation
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“1 P14 TCR transgenic mice have been described previously (29).”
BackgroundSelf-citation
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Background
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Background
Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes
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Self-citation
Autocrine and paracrine IL-2 signals collaborate to regulate distinct phases of CD8 T cell memory
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Constitutive Expression of IL-7 Receptor α Does Not Support Increased Expansion or Prevent Contraction of Antigen-Specific CD4 or CD8 T Cells following Listeria monocytogenes Infection
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“Expression of IL-7R by a small frequency of effector CD8 T cells at the peak of Ag-induced expansion has been suggested to permit these cells to survive the contraction phase and become memory Ag-specific CD8 T cells (6, 7).”
Background
Pharmacologic Induction of CD8 + T Cell Memory: Better Living Through Chemistry
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Rejuvenation of the aging T cell compartment
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Active Evasion of CTL Mediated Killing and Low Quality Responding CD8+ T Cells Contribute to Persistence of Brucellosis
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“These markers can be used to distinguish naı̈ve CD8+ T cells (LFA1 CD127 KLRG1), early effectors (LFA1 CD127 KLRG1), short-lived effectors (LFA1 CD127 KLRG1), and CD8+ Tmem (LFA1 CD127 KLRG1) [48,49,50,51].”
Background
Cell-to-Cell Variability Analysis Dissects the Plasticity of Signaling of Common γ Chain Cytokines in T Cells
Cotari, J. W., Voisinne, G., Dar, O. E., Karabacak, V., & Altan-Bonnet, G. Y. (2013) · Science Signaling · doi:10.1126/scisignal.2003240 · Cited by 61
“A decrease in IL-7R abundance or signaling does not account for the observed increase in IL-7 EC50 The effect of IL-2Ra abundance on IL-7 EC50 could be hypothesized to stem from the reported inverse correlation between IL-2Ra and IL-7Ra abundances during the course of differentiation from naïve to effector to memory p…”
BackgroundMethod
IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection
Renkema, K. R., Lee, J., Lee, Y. J., Hamilton, S. E., Hogquist, K. A., & Jameson, S. C. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151359 · Cited by 61
“Elevated T-bet expression levels are required for effective generation of SLECs, identified in LCMV infections by a CD127 KLRG1 phenotype, whereas MPECs identified as CD127 KLRG1 are more likely to survive contraction and develop into long-lived memory cells (Kaech et al., 2003).”
Background
Divergent Generation of Heterogeneous Memory CD4 T Cells
Moulton, V. R., Bushar, N. D., Leeser, D. B., Patke, D. S., & Färber, D. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.869 · Cited by 61
“Although it was shown that the IL-7R expression during the peak effector stage marks the cellular precursors to virus-specific memory CD8 T cells (8), this correlation has not been upheld for peptide-primed CD8 T cells (10), and its role in memory CD4 T cell generation is not defined.”
Background
Signaling control of memory T cell generation and function
Chandok, M. R., & Färber, D. L. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.08.009 · Cited by 61
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“Consistent with recent publications (21), at 7 days following immunization expression of IL-7R was decreased on tetramer-positive cells compared to CD3 CD8 tetramer-negative cells, a population that would include primarily naïve cells but also a small population of activated cells (Fig.”
BackgroundInfluential
Hantaan Virus Infection Induces Both Th1 and ThGranzyme B+ Cell Immune Responses That Associated with Viral Control and Clinical Outcome in Humans
Ma, Y., Yuan, B., Zhuang, R., Zhang, Y., Liu, B., Zhang, C., Zhang, Y., Yu, H., Yi, J., Yang, A., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004788 · Cited by 60
“CD127 is known highly expressed on T cells and is considered as a marker for memory precursor CD8T cells during viral infection [64].”
Background
Reduced Functional Avidity Promotes Central and Effector Memory CD4 T Cell Responses to Tumor-Associated Antigens
Caserta, S., Kleczkowska, J., Mondino, A., & Zamoyska, R. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001867 · Cited by 64
“CD127 expression has been linked to the survival of CD4+ memory cells (37), and in CD8 effector cells CD127 expression has been reported to indicate that these cells are destined to enter the TCM pool (38).”
Background
Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients
Lasso, P., Mateus, J., Pavia, P. X., Rosas, F., Roa, N. L., Thomas, M. C., López, M. C., González, J. M., Puerta, C. J., & Cuéllar, A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500459 · Cited by 61
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Jung, Y. W., Kim, H. G., Perry, C. J., & Kaech, S. M. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602899113 · Cited by 59
“fluorescein succinimidyl ester (CFSE; Invitrogen) as described previously (26).”
MethodSelf-citation
Pulmonary immunity to viruses
Allie, S. R., & Randall, T. D. (2017) · Clinical Science · doi:10.1042/cs20160259 · Cited by 63
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Schmidt, M. E., & Varga, S. M. (2018) · Cytokine · doi:10.1016/j.cyto.2018.07.012 · Cited by 61
“1c) [51, 52] .”
Listeria monocytogenes: Pathogenesis and Host Response
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Down‐Regulation of Interleukin‐7 Receptor (CD127) in HIV Infection Is Associated with T Cell Activation and Is a Main Factor Influencing Restoration of CD4+Cells after Antiretroviral Therapy
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“As previously observed in multiple infection models, including LCMV infection of WT mice (35), IL-7R (CD127) expression was down-regulated at day 8 on GP33-specific IFN- producing effector CD8 T cells in both groups of mice.”
Method
Persistence of Transgene Expression Influences CD8+T-Cell Expansion and Maintenance following Immunization with Recombinant Adenovirus
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“Indeed, several reports have suggested that memory cells can be generated within the first few days of a primary response (3, 22, 47).”
Background
Additive effects of CpG ODN and R-848 as adjuvants on augmenting immune responses to HBsAg vaccination
Ma, R., Du, J.-L., Huang, J., & Wu, C. Y. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.028 · Cited by 59
Effector T Cell Differentiation and Memory T Cell Maintenance Outside Secondary Lymphoid Organs
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Clinical strategies to enhance T cell reconstitution
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Human Granzyme K Is a Feature of Innate T Cells in Blood, Tissues, and Tumors, Responding to Cytokines Rather than TCR Stimulation
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Programmed Death-1 Shapes Memory Phenotype CD8 T Cell Subsets in a Cell-Intrinsic Manner
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“It is pertinent, therefore, that ∼60% of vaccine-induced NS3514–531 epitope-specific memory CD8 T cells expressed the cell surface marker CD127, which is associated with long-term maintenance of T cell memory (36) and correlates with a successful virologic FIGURE 6.”
Background
Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b
Zhang, S., Rozell, M., Verma, R. K., Albu, D. I., Califano, D., VanValkenburgh, J., Merchant, A., Rangel‐Moreno, J., Randall, T. D., Jenkins, N. A., et al. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20092136 · Cited by 58
“…the effector cells produce less perforin and granzyme One cause for the poor Ag-specific cytolytic activity of Bcl11b-deficient CTLs might be defective differentiation into short-lived effector cells, which up-regulate Klrg1 and down-regulate CD127, during the immune response (Kaech et al., 2003).”
Background
Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T‐cells and tumour cells
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“…CTLs which is composed of memory precursor cells and short-lived effector cells, the latter of which destined to die after pathogens are cleared (Huster et al., 2004; Joshi et al., 2007; Kaech et al., 2003; Kalia & Sarkar, 2018; Kalia et al., 2010; Sarkar et al., 2008; Shrikant et al., 2010).”
Background
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IL-15-Independent Proliferative Renewal of Memory CD8+ T Cells in Latent Gammaherpesvirus Infection
Obar, J. J., Crist, S. G., Leung, E. K., & Usherwood, E. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.4.2705 · Cited by 58
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van Leeuwen, E. M. M., de Bree, G. J., ten Berge, I. J. M., & van Lier, R. A. W. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00379.x · Cited by 57
“CD127 or IL-7Ra is expressed by all naı̈ve T cells in both mice and humans (26).”
BackgroundInfluential
Establishment and recall of CD8+ T‐cell memory in a model of localized transient infection
Kedzierska, K., Gruta, N. L. L., Turner, S. J., & Doherty, P. C. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00386.x · Cited by 59
“Furthermore, though the published evidence (11) suggests that IL-7Ra expression identifies the precursors of CD8 memory T cells at the acute phase of infection, our data showing that up to 70% of the DPA224 CD8 and 38% of the DNP366 CD8 T cells express IL-7Ra at the peak of the primary response indicate that (as there…”
Background
Low Frequency of Circulating CD8+ T Stem Cell Memory Cells in Chronic Chagasic Patients with Severe Forms of the Disease
Mateus, J., Lasso, P., Pavia, P. X., Rosas, F., Roa, N. L., Valencia‐Hernández, C. A., González, J. M., Puerta, C. J., & Cuéllar, A. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0003432 · Cited by 57
Ever closer to a prophylactic vaccine for HCV
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“Effector T cells have been divided into memory precursor effector cells and short-lived effector cells by their expression of CD127 (IL-7Ra), and KLRG1 and a population of T cells with stem cell-like properties have been described (Tscm) [126-128].”
Background
Identification of FABP5 as an immunometabolic marker in human hepatocellular carcinoma
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Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells
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Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia
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Stable CD8+ T Cell Memory during Persistent Trypanosoma cruzi Infection
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“tined to become long-lived TCM cells (9) capable of self renewal and rapid recall to Ag (10).”
Background
Adoptive T-cell therapy for HBV-associated HCC and HBV infection
Tan, A. T., & Schreiber, S. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104748 · Cited by 58
Molecular characterization of HCMV‐specific immune responses: Parallels between CD8+ T cells, CD4+ T cells, and NK cells
Braga, F. A. V., Hertoghs, K. M. L., van Lier, R. A. W., & van Gisbergen, K. P. J. M. (2015) · European Journal of Immunology · doi:10.1002/eji.201545495 · Cited by 56
Immunotherapeutic effects of IL-7 during a chronic viral infection in mice
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A Novel Role of CD30L/CD30 Signaling by T-T Cell Interaction in Th1 Response against Mycobacterial Infection1
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Long-Lasting Cross-Protection Against Influenza A by Neuraminidase and M2e-based immunization strategies
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IL-12-Programmed Long-Term CD8+ T Cell Responses Require STAT4
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“In fact, the loss of IL-15 reduces CD8 memory generation and IL-7R expression on effector is considered as a marker for future memory cells (17, 18).”
Background
Augmented IL-7 Signaling during Viral Infection Drives Greater Expansion of Effector T Cells but Does Not Enhance Memory
Sun, J. C.-Y., Lehar, S. M., & Bevan, M. J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4458 · Cited by 56
“them as memory precursors, and IL-7 signaling protects them from apoptosis, allowing their survival to become long-lived memory T cells (22, 24).”
Background
Bone marrow‐derived cells expand memory CD8+ T cells in response to viral infections of the lung and skin
Belz, G. T., Wilson, N. S., Smith, C. M., Mount, A. M., Carbone, F. R., & Heath, W. R. (2006) · European Journal of Immunology · doi:10.1002/eji.200535432 · Cited by 56
CD8+ T-cell memory: only the good ones last
Northrop, J. K., & Shen, H. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.05.004 · Cited by 56
Human skin-resident host T cells can persist long term after allogeneic stem cell transplantation and maintain recirculation potential
de Almeida, G. P., Lichtner, P., Eckstein, G., Brinkschmidt, T., Chu, C.-F., Sun, S., Reinhard, J., Mädler, S. C., Kloeppel, M., Verbeek, M., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abe2634 · Cited by 58
Activation-induced non-responsiveness (anergy) limits CD8 T cell responses to tumors
Mescher, M. F., Popescu, F. E., Gerner, M. Y., Hammerbeck, C. D., & Curtsinger, J. (2007) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2007.06.008 · Cited by 55
“[77] showed that the small population of CD8 effector cells that were IL-7Rα high at the peak of a response to LCMV were the cells that could survive long term to become memory cells, while subsequent work showed that not all IL-7Rα high cells present at the peak of a response survived long term ([78–80] and Hammerbec…”
Background
Human and Murine Obliterative Bronchiolitis in Transplant
McDyer, J. F. (2007) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200605-107jg · Cited by 54
IL‐10 promotes homeostatic proliferation of human CD8 + memory T cells and, when produced by CD1c + DCs, shapes naive CD8 + T‐cell priming
Nizzoli, G., Larghi, P., Paroni, M., Crosti, M., Moro, M., Neddermann, P., Caprioli, F., Pagani, M., Francesco, R. D., Abrignani, S., et al. (2016) · European Journal of Immunology · doi:10.1002/eji.201546136 · Cited by 55
The immune battlefield: The impact of inflammatory cytokines on CD8+ T-cell immunity
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CXCR3 Identifies Human Naive CD8+ T Cells with Enhanced Effector Differentiation Potential
De Simone, G., Mazza, E. M. C., Cassotta, A., Davydov, A. N., Kuka, M., Zanon, V., De Paoli, F., Scamardella, E., Metsger, M., Roberto, A., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1901072 · Cited by 49
“Once this process is complete, small numbers of Ag-specific T cells survive and become long-lived memory T (TMEM) cells (7), which exhibit diverse epigenetic, functional, metabolic, and transcriptional properties (8–13).”
Background
T Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323
Integrating Genomic Signatures for Immunologic Discovery
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Self-citation
Proliferation Capacity and Cytotoxic Activity Are Mediated by Functionally and Phenotypically Distinct Virus-Specific CD8 T Cells Defined by Interleukin-7Rα (CD127) and Perforin Expression
Cellerai, C., Perreau, M., Rozot, V., Enders, F. B., Pantaleo, G., & Harari, A. (2010) · Journal of Virology · doi:10.1128/jvi.02565-09 · Cited by 54
“Moreover, it was shown in mice (34, 36) and humans (14, 48, 63) that the CD127 memory-precursor CD8 T cells produced IL-2 in contrast to CD127 effector CD8 T cells.”
BackgroundInfluential
Quality of the Transgene-Specific CD8+ T Cell Response Induced by Adenoviral Vector Immunization Is Critically Influenced by Virus Dose and Route of Vaccination
Holst, P. J., Ørskov, C., Thomsen, A. R., & Christensen, J. P. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0900537 · Cited by 54
Live Attenuated Leishmania donovani Centrin Gene–Deleted Parasites Induce IL-23–Dependent IL-17–Protective Immune Response against Visceral Leishmaniasis in a Murine Model
Banerjee, A., Bhattacharya, P., Dagur, P. K., Karmakar, S., Ismail, N., Joshi, A. B., Akue, A. D., KuKuruga, M. A., McCoy, J. P., Dey, R., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700674 · Cited by 54
“Importantly, in the absence of IL-23R, activated Th17 cells retain low IL-7Ra expression, known to be important for the survival of memory CD8 T cells (79).”
Background
CD8+ Resident Memory T Cells and Viral Infection
Wu, X., Wu, P., Shen, Y., Jiang, X., & Xu, F. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02093 · Cited by 57
“CD127 killer cell lectin-like receptor G1 (KLRG1) CD8 T cells have been demonstrated to be memory precursor effector cells (MPECs) (56).”
Background
CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals
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Rapid Development of T Cell Memory
Wong, P., Lara-Tejero, M., Ploß, A., Leiner, I. M., & Pamer, E. G. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7239 · Cited by 54
“Our results are consistent with recent data indicating that memory cell precursors can be found amid the primary response (11).”
BackgroundResult
Brain Resident Memory T Cells Rapidly Expand and Initiate Neuroinflammatory Responses Following CNS Injury and Viral InfectionPreprint
Ayasoufi, K., Wolf, D. M., Namen, S. L., Jin, F., Tritz, Z. P., Pfaller, C. K., Zheng, J., Goddery, E. N., Fain, C. E., Gulbicki, L. R., et al. (2022) · SSRN Electronic Journal · doi:10.1016/j.bbi.2023.05.009 · Cited by 54
Technology meets TILs: Deciphering T cell function in the -omics era
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Significance of Preexisting Vector Immunity and Activation of Innate Responses for Adenoviral Vector-Based Therapy
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Background
Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data
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“While IL7R is downregulated in most CD8 + effector cells, it can be indicative of memory precursor effector cells (MPECs) which survive after viral clearing to form a long-lasting immune memory 47 .”
Continuous expression of TOX safeguards exhausted CD8 T cell epigenetic fate
Huang, Y., Ngiow, S. F., Baxter, A. E., Manne, S., Park, S. L., Wu, J. E., Khan, O., Giles, J. R., & Wherry, E. J. (2025) · Science Immunology · doi:10.1126/sciimmunol.ado3032 · Cited by 57
Self-citation
PD-1 and Tim-3 Pathways Regulate CD8+ T Cells Function in Atherosclerosis
Qiu, M., Wang, S., Dai, Y., Wang, S., Ou, J., & Quan, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0128523 · Cited by 54
“CD8 TCM cells are less cytolytic and exhibit increased ability of self-renewal compared to CD8 + TEM cells[33,34,35].”
Age-Related CD8+ T Cell Clonal Expansions Express Elevated Levels of CD122 and CD127 and Display Defects in Perceiving Homeostatic Signals
Messaoudi, I., Warner, J., & Nikolich‐Žugich, J. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.5.2784 · Cited by 53
“IL-15 is the main maintenance factor for memory T cells (24), and it has been shown that IL-7, whose receptor is expressed on all naive and memory, but not activated, T cells (25), can substitute for its action in IL-15-deficient animals (26).”
Background
Reduced Protection from Simian Immunodeficiency Virus SIV mac251 Infection Afforded by Memory CD8 + T Cells Induced by Vaccination during CD4 + T-Cell Deficiency
Vaccari, M., Mattapallil, J. J., Song, K., Tsai, W.-P., Hryniewicz, A., Venzon, D. J., Zanetti, M., Reimann, K. A., Roederer, M., & Franchini, G. (2008) · Journal of Virology · doi:10.1128/jvi.00893-08 · Cited by 53
“Effector T-cell populations at the peak of CD8 T-cell responses are programmed to undergo antigen-independent contraction, with a small portion of these cells persisting to constitute the long-term memory T-cell population (22, 41, 49).”
Background
Mcl-1 antagonizes Bax/Bak to promote effector CD4+ and CD8+ T-cell responses
Tripathi, P., Koss, B. S., Opferman, J. T., & Hildeman, D. A. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.25 · Cited by 53
“levels of Bcl-2 are decreased, whereas Bcl-xL expression is increased.(13,15,16) However, despite the normal induction of Bcl-xL, T cell-specific genetic deletion of Bcl-xL did not exacerbate the contraction of CD4þ or CD8þ T cell responses,(17) suggesting that either Bcl-xL is not required for effector T-cell surviva…”
Background
Soluble multi-trimeric TNF superfamily ligand adjuvants enhance immune responses to a HIV-1 Gag DNA vaccine
Kanagavelu, S. K., Snarsky, V., Termini, J. M., Gupta, S., Barzee, S., Wright, J. A., Khan, W. N., Kornbluth, R. S., & Stone, G. W. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.11.088 · Cited by 53
“Maintaining a population of virus specific memory T cells is crucial to protect against re-infection [59].”
Characterization of the Specificity, Functionality, and Durability of Host T‐Cell Responses Against the Full‐Length Hepatitis E Virus
Brown, A., Halliday, J., Swadling, L., Madden, R. G., Bendall, R. P., Hunter, J. G., Maggs, J., Peter Simmonds, K., Smith, D. B., Vine, L. J., et al. (2016) · Hepatology · doi:10.1002/hep.28819 · Cited by 53
“IL-7 signaling is an important survival signal for memory T cells, and the expression of its receptor, CD127, is characteristic of long-lived memory T cells.((52-55)) HEV-specific T cells assessed here were predominantly CD127(1) and were a mixed population of central (Tcm) and effector memory (Tem) subsets, with litt…”
Background
Protective immunity to liver‐stage malaria
Holz, L. E., Fernandez‐Ruiz, D., & Heath, W. R. (2016) · Clinical & Translational Immunology · doi:10.1038/cti.2016.60 · Cited by 53
Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function
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“Finally, a landmark study by Kaech and colleagues identified cell surface markers on effector CD8+ T cells that allow phenotypic identification of short-lived effector cells (SLEC) and memory precursor effector cells (MPEC) early in the immune response (Kaech et al., 2003).”
Background
Memory T Cell Dynamics in the Lung during Influenza Virus Infection
Pizzolla, A., & Wakim, L. M. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1800979 · Cited by 57
“Whether an effector T cell transitions into a memory cell is influenced by early events occurring during T cell priming (66), which see KLRG1lo CD127(IL-7Ra)lo effector cells segregating into either terminally differentiated short-lived effector T cells (KLRG1hi and CD127lo) or memory precursors T cells (KLRG1lo CD127…”
Background
Gammaherpesvirus Persistence Alters Key CD8 T-Cell Memory Characteristics and Enhances Antiviral Protection
Obar, J. J., Fuse, S., Leung, E. K., Bellfy, S. C., & Usherwood, E. J. (2006) · Journal of Virology · doi:10.1128/jvi.00237-06 · Cited by 53
“The expression of these molecules was similar to what was observed for memory CD8 T cells reactive against vaccinia virus (data not shown) and is similar to what was observed during acute and chronic LCMV infection (26, 57).”
BackgroundResult
Loss of IL-7 Receptor α on CD4+ T Cells Defines Terminally Differentiated B Cell-Helping Effector T Cells in a B Cell-Rich Lymphoid Tissue
Lim, H. W., & Kim, C. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.11.7448 · Cited by 54
Phenotypic and functional profiling of malaria-induced CD8 and CD4 T cells during blood-stage infection with Plasmodium yoelii
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Self-citation
Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune Therapies for Cancer
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Regulation of Inflammatory Chemokine Receptors on Blood T Cells Associated to the Circulating Versus Liver Chemokines in Dengue Fever
de‐Oliveira‐Pinto, L. M., Marinho, C. F., Póvoa, T. F., de Azeredo, E. L., de Souza, L. A., Barbosa, L. D. R., Motta-Castro, A. R. C., Alves, A. M. B., Ávila, C. A. L., de Souza, L. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038527 · Cited by 54
“Among them are CD29 (b1) integrin that include VLA-4 (CD49d/CD29) [13,39] Similarly, T cell migration CD44 receptor is a glycoprotein ascribed for having a role in lymphocyte homing to sites of inflammation [40,41] Furthermore, signals emanating from the cytokine receptor for IL-7 (CD127) are particularly critical for…”
Background
Early CD8 T-cell memory precursors and terminal effectors exhibit equipotent in vivo degranulation
Yuzefpolskiy, Y., Baumann, F. M., Kalia, V., & Sarkar, S. (2014) · Cellular and Molecular Immunology · doi:10.1038/cmi.2014.48 · Cited by 52
HIV-specific CD8 T cells express low levels of IL-7Rα: Implications for HIV-specific T cell memory
Wherry, E. J., Day, C. L., Draenert, R., Miller, J. D., Kiepiela, P., Woodberry, T., Brander, C., Addo, M. M., Klenerman, P., Ahmed, R., et al. (2006) · Virology · doi:10.1016/j.virol.2006.06.017 · Cited by 52
“The expression of CD127 (IL-7Rα) plays a key role in antigenindependent memory CD8 T cell homeostasis following acute infection or vaccination (Goldrath et al., 2002; Kaech et al., 2003; Schluns et al., 2000; Wherry et al., 2004).”
BackgroundInfluentialSelf-citation
Cytokine-dependent regulation of NADPH oxidase activity and the consequences for activated T cell homeostasis
Purushothaman, D., & Sarin, A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082851 · Cited by 50
“Although challenged by recent studies (Kaech et al., 2003; Badovinac et al., 2004), contraction of activated T cells is thought to be triggered by competition for limiting amounts of cytokine in the waning phase of the immune response.”
Background

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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