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Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells
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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“Ag-specific CD8 T cells derived from the effector phase of a response can express various combinations of CD127 and KLRG1, which define either more short-lived effector cells (SLECs; CD127−KLRG1+), which are lost during the contraction phase of the immune response, or memory precursor effector cells (MPECs; CD127+KLRG1−), which are more likely to persist and contribute to memory populations [224,”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [224]
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Self-citationLymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine
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“Further fractionation of the effector CD8 T cells into KLRG1 IL-7Ra terminal effector and KLRG1 IL-7Ra memory precursor effector cell subsets at 14 dpi revealed that AQP9 was selectively expressed in the IL-7Ra effector cells that preferentially seed the memory T cell pool (Figure 1C) (Kaech et al., 2003; Schluns et a…”
InfluentialSelf-citationBACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers
Roychoudhuri, R., Clever, D. C., Li, P., Wakabayashi, Y., Quinn, K. M., Klebanoff, C. A., Ji, Y., Sukumar, M., Eil, R. L., Yu, Z., et al. (2016) · Nature Immunology · doi:10.1038/ni.3441 · Cited by 317
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CD8+ T cell contraction is controlled by early inflammation
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Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination
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Self-citationT-cell homing specificity and plasticity: new concepts and future challenges
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Self-citationPD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells
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“press CD127 are preferentially destined to become memory CD8 T cells (50).”
Self-citationFeatures of responding T cells in cancer and chronic infection
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“Analyses using acute viral models have led to the elucidation of immunological T cell memory, a cardinal property of adaptive immunity, as re-exposure to the same pathogen results in more rapid and robust T cell responses [1-6].”
BackgroundSelf-citationLinoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity
Lauson, C. B. N., Tiberti, S., Corsetto, P. A., Conte, F., Tyagi, P., Machwirth, M., Ebert, S., Loffreda, A., Scheller, L., Sheta, D., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.02.013 · Cited by 302
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Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells
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Self-citationGeneration of effector CD8 + T cells and their conversion to memory T cells
Cui, W., & Kaech, S. M. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00926.x · Cited by 299
“Naive CD8 T cells express IL-7R, but IL-7R expression precipitously falls on activated CD8 T cells as they expand and differentiate during infection (21, 23, 29, 151).”
BackgroundSelf-citationAngelosanto, J., Blackburn, S. D., Crawford, A., & Wherry, E. J. (2012) · Journal of Virology · doi:10.1128/jvi.00889-12 · Cited by 285
“During acute infection, memory CD8 T cells arise from a subpopulation of CD127 KLRG1 memory precursors, while another subpopulation of terminally differentiated (CD127 KLRG1) effector CD8 T cells gradually dies off (18, 20).”
BackgroundSelf-citationHarari, A., Vallelian, F., Meylan, P. R., & Pantaleo, G. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.2.1037 · Cited by 284
“Recent studies (24) have shown that a small proportion of effector cells expressing the IL-7R serves as precursors for memory CD8 T cells after Ag clearance.”
BackgroundPD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells
Deak, L. C., Nicolini, V., Hashimoto, M., Karagianni, M., Schwalie, P. C., Lauener, L., Varypataki, E. M., Richard, M., Bommer, E., Sam, J., et al. (2022) · Nature · doi:10.1038/s41586-022-05192-0 · Cited by 286
Self-citationNdhlovu, Z. M., Kamya, P., Mewalal, N., Kløverpris, H. N., Nkosi, T., Pretorius, K., Laher, F., Ogunshola, F. J., Chopera, D., Shekhar, K., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.08.012 · Cited by 282
Combining immunotherapy and anticancer agents: the right path to achieve cancer cure?
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“All analyzed T cells were also negative for CD127 (data not shown).”
BackgroundInfluentialSiegel, A., Heimall, J. R., Freeman, A. F., Hsu, A. P., Brittain, E., Brenchley, J. M., Douek, D. C., Fahle, G. H., Cohen, J. I., Holland, S. M., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.016 · Cited by 284
“I CD127, an important central memory surface marker (Kaech et al., 2003), was lower in AD-HIES central memory T cells (Figures 1D, 1E, and S1E).”
BackgroundInfluentialDominguez, C. X., Amezquita, R. A., Guan, T., Marshall, H. D., Joshi, N. S., Kleinstein, S. H., & Kaech, S. M. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150186 · Cited by 275
“Class I MHC tetramers were generated as described previously (Kaech et al., 2003).”
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“Adoptively transferred CD127 CD8 T but not CD127 CD8 T cells survived in the absence of Ag by homeostatic proliferation and thus maintenance via CD127 (13, 22).”
BackgroundInfluentialEgawa, T., Tillman, R. E., Naoe, Y., Taniuchi, I., & Littman, D. R. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070133 · Cited by 276
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“These latter molecules all play key roles in the homeostasis and survival of long-lived memory CD8 T cells (Castellino and Germain, 2007; Hendriks et al., 2003; Kaech et al., 2003).”
BackgroundViral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection
Shin, H., Blackburn, S. D., Blattman, J. N., & Wherry, E. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061937 · Cited by 273
“from the supernatant of the A7R34 hybridoma and used as described (20).”
MethodSelf-citationFunctional signatures of protective antiviral T‐cell immunity in human virus infections
Harari, A., Dutoit, V., Cellerai, C., Bart, P., Pasquier, R. D., & Pantaleo, G. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00395.x · Cited by 272
“recent study performed in mice has shown that the selective expression of the IL-7 receptor-a (CD127) identifies effector CD8 T cells that give rise to long-lived antigen-specific T cells (83).”
BackgroundLalli, P. N., Strainic, M. G., Yang, M., Lin, F., Medof, M. E., & Heeger, P. S. (2008) · Blood · doi:10.1182/blood-2008-04-151068 · Cited by 271
IL-7: maintaining T-cell memory and achieving homeostasis
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Form follows function: lymphoid tissue microarchitecture in antimicrobial immune defence
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Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey
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Contributions of humoral and cellular immunity to vaccine-induced protection in humans
Amanna, I. J., & Slifka, M. K. (2011) · Virology · doi:10.1016/j.virol.2010.12.016 · Cited by 263
“Likewise, the surface antigens, KLRG1 and CD127, have been used extensively to subdivide effector and memory T cell subsets and these phenotypic markers are useful for predicting whether the virus (or vaccine) induces primarily short-lived memory (KLRG1+ CD127-) or long-lived memory (KLRG1−CD127+) T cell responses (Cu…”
BackgroundGiles, J. R., Ngiow, S. F., Manne, S., Baxter, A. E., Khan, O., Wang, P., Staupe, R., Abdel-Hakeem, M. S., Huang, H., Mathew, D., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01338-4 · Cited by 264
Self-citationPrecursors of human CD4 + cytotoxic T lymphocytes identified by single-cell transcriptome analysis
Patil, V. S., Madrigal, A., Schmiedel, B. J., Clarke, J., O’Rourke, P., de Silva, A. D., Harris, E., Peters, B., Seumois, G., Weiskopf, D., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aan8664 · Cited by 262
“The opposing expression pattern of KLRG1 and IL7R transcripts in clusters 3 and 4 is similar to that observed in memory precursor effector cells (IL-7Rhigh and KLRG1−) described in murine models of resolving acute infections (52, 56).”
ResultInterleukin‐2 in the development and control of inflammatory disease
Hoyer, K. K., Dooms, H., Barron, L., & Abbas, A. K. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00697.x · Cited by 259
“It has also become clear that upon activation, T cells lose IL-7Ra expression (16, 23, 27).”
BackgroundZammit, D. J., Turner, D., Klonowski, K. D., Lefrançois, L., & Cauley, L. S. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.015 · Cited by 262
“As an additional indicator of TcR-mediated activation, we analyzed IL-7R (CD127) expression, because this receptor is expressed by naive T cells and resting memory T cells but is downregulated after activation (Schluns et al., 2000; Kaech et al., 2003; Huster et al., 2004; Lang et al., 2005).”
MethodMolecular Signatures Distinguish Human Central Memory from Effector Memory CD8 T Cell Subsets
Willinger, T., Freeman, T. C., Hasegawa, H., McMichael, A. J., & Callan, M. F. C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.5895 · Cited by 256
“For example, naive CD8 T cells were characterized by higher expression of receptors for IL-6 ( IL-6ST ) and IL-7 ( IL-7R ).”
InfluentialIto, M., Maruyama, T., Saito, N., Koganei, S., Yamamoto, K., & Matsumoto, N. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051986 · Cited by 260
“Although T cell expression of KLRG1 in normal mice is restricted to small subpopulations of eff ector–memory type T cells (11, 12, 15), expression of KLRG1 is upregulated in mouse CD8+ T cells by infection with pathogens (12, 16).”
BackgroundOmilusik, K. D., Best, J. A., Yu, B., Goossens, S., Weidemann, A., Nguyen, J. V., Seuntjens, E., Stryjewska, A., Zweier, C., Roychoudhuri, R., et al. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20150194 · Cited by 260
“Both subsets express high levels of CD44, whereas IL-7-receptor-α (CD127) is selectively up-regulated during the transition to long-lived memory cells (Kaech et al., 2003).”
BackgroundEffector-like CD8+ T Cells in the Memory Population Mediate Potent Protective Immunity
Olson, J. A., McDonald-Hyman, C. S., Jameson, S. C., & Hamilton, S. E. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.009 · Cited by 262
“However, in contrast to the drastic downregulation of CD127 reported for short-lived effector cells (Joshi et al., 2007; Kaech et al., 2003; Obar and Lefrançois, 2010), the memory stage CD27lo CD43lo population expressed CD127 at levels similar to naive CD8+ T cells (albeit at lower levels than…”
BackgroundInfluentialChijioke, O., Mueller, A., Feederle, R., Barros, M. H. M., Krieg, C., Emmel, V. E., Marcenaro, E., Leung, C. S. K., Antsiferova, O., Landtwing, V., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.11.041 · Cited by 259
“Activated memory T cells weremainly foundwithin theCD8 T cell compartment in infected animals (Figures S2A andS2B) and expanded at the cost of naive CD8 T cell frequencies with NK cell depletion significantly affecting CX3CR1 upregulation and expansion of CD11a CD127 CD8 T cells, which in mice have been proposed to be…”
BackgroundRegional and mucosal memory T cells
Sheridan, B. S., & Lefrançois, L. (2011) · Nature Immunology · doi:10.1038/ni.2029 · Cited by 268
“The fate of effector CD8 + T cells has been identified by expression of the receptors KLRG1 (killer cell lectin-like receptor subfamily G1) and CD127 (interleukin 7 (IL-7) receptor α-chain”
IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis
Carrette, F., & Surh, C. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.010 · Cited by 257
“During viral infection, the memory-precursor effector cells (MPEC; CD127hi KLRG1lo) regain CD127 expression, as opposed to the short-lived effector cells (SLEC; CD127lo KLRG1hi) [75], thereby making CD127 a marker for memory precursor CD8 T cells.”
BackgroundSelf-citationEpigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation
Yu, B., Zhang, K., Milner, J. J., Toma, C., Chen, R., Scott-Browne, J. P., Pereira, R. M., Crotty, S., Chang, J. T., Pipkin, M. E., et al. (2017) · Nature Immunology · doi:10.1038/ni.3706 · Cited by 248
Memory CD4 T cells emerge from effector T-cell progenitors
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Inflaming the CD8+ T Cell Response
Haring, J. S., Badovinac, V. P., & Harty, J. T. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.001 · Cited by 264
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Self-citationCellular metabolism regulates the differentiation and function of T-cell subsets
Ma, S., Ming, Y., Wu, J., & Cui, G. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01148-8 · Cited by 276
“Circulating memory T cells, which are characterized by high expression of interleukin-7 (IL-7), R α and IL-15R β , endure for extended periods, often years, and offer sustained and long-lasting protection against reinfection [40 – 42].”
BackgroundAdjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool
Melchionda, F., Fry, T. J., Milliron, M., McKirdy, M. A., Tagaya, Y., & Mackall, C. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23134 · Cited by 245
“A consistent theme from recent studies of immune effector and memory cell biology is the critical roles of γc cytokines in general and of IL-7 and IL-15 in particular (9, 11, 16, 19, 48).”
BackgroundJoshi, N. S., & Kaech, S. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1309 · Cited by 245
“For example, following acute LCMV infection the expression of KLRG1 and IL-7R appears quite stable and little conversion is observed between the SLEC and MPEC subsets (23, 30).”
BackgroundInfluentialSelf-citationRegulation of innate CD8 + T-cell activation mediated by cytokines
Freeman, B. E., Hammarlund, E., Raué, H.-P., & Slifka, M. K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203543109 · Cited by 244
“This result is not unexpected because IL-7R (CD127) is expressed by only a small subset of LCMV-specific T cells at the peak of the primary CD8 T-cell response (25).”
BackgroundStreeck, H., Brumme, Z. L., Anastario, M. P., Cohen, K. W., Jolin, J. S., Meier, A., Brumme, C. J., Rosenberg, E. S., Alter, G., Allen, T. M., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050100 · Cited by 241
“Similarly, differences between antigen-specific CD8þ T cells from HIV-1 progressors and nonprogressors with respect to up-regulation of programmed death-1 (PD-1, also called CD279) [18–21] and downmodulation of the IL-7 receptor in chronic viral infection (CD127) [22,23] have been demonstrated.”
BackgroundInfluentialImproving T Cell Therapy for Cancer
Leen, A. M., Rooney, C. M., & Foster, A. E. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141527 · Cited by 240
Targeting memory T cell metabolism to improve immunity
Corrado, M., & Pearce, E. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148546 · Cited by 250
Mortier, E., Advincula, R., Kim, L., Chmura, S. A., Barrera, J., Reizis, B., Malynn, B. A., & Ma, A. I. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.017 · Cited by 236
“IL-7 signals to CD8+ T cells may support this transition of effector CD8+ T cells to memory CD8+ T cells (Kaech et al., 2003; Hand et al., 2007).”
BackgroundThe epigenetic control of stemness in CD8 + T cell fate commitment
Pace, L., Goudot, C., Zueva, E., Gueguen, P., Burgdorf, N., Waterfall, J. J., Quivy, J., Almouzni, G., & Amigorena, S. (2018) · Science · doi:10.1126/science.aah6499 · Cited by 232
Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals
Paiardini, M., Cervasi, B., Albrecht, H., Muthukumar, A., Dunham, R. M., Gordon, S. N., Radziewicz, H., Piedimonte, G., Magnani, M., Montroni, M., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.5.2900 · Cited by 233
Self-citationChoi, Y. S., Kotov, J. A., Yusuf, I., Johnston, R. J., Greenbaum, J., Peters, B., & Crotty, S. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202963 · Cited by 243
“All mice were housed in ventilated racks with HEPA filters and provided with irradiated PicoLab Rodent Diet (20-5053) food.”
BackgroundMethodInfluentialSoares, A. P., Scriba, T. J., Joseph, S., Harbacheuski, R., Murray, R. A., Gelderbloem, S., Hawkridge, A., Hussey, G. D., Maecker, H. T., Kaplan, G., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3569 · Cited by 231
Generation and maintenance of immunological memory
Gourley, T. S., Wherry, E. J., Masopust, D., & Ahmed, R. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.08.013 · Cited by 241
Self-citationType I Interferon Protects Antiviral CD8+ T Cells from NK Cell Cytotoxicity
Xu, H. C., Grusdat, M., Pandyra, A. A., Polz, R., Huang, J., Sharma, P., Deenen, R., Köhrer, K., Rahbar, R., Diefenbach, A., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.004 · Cited by 232
“Furthermore, we observed higher expression of PD-1 and lower expression of KLRG1 in Ifnar1–/–”
BackgroundResultInfluentialImmunological memory in humans
Crotty, S., & Ahmed, R. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.02.008 · Cited by 231
“It appears that then an IL-7Rhi subset of effector cells differentiate to become memory T cells [36,38].”
Self-citationWang, S., Campos, J. S., Gallotta, M., Gong, M., Crain, C., Naik, E., Coffman, R. L., & Guiducci, C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608555113 · Cited by 235
“Tumors responding to anti–PD-1 alone or to the combination treatment harbor a significantly increased number of antigen-specific CD8+ T cells with the MPEC phenotype, whereas the SD-101 alone-treated group is highly enriched in CD8+ T cells with a SLEC phenotype (Fig.”
BackgroundInfluentialGeneration of CD8 T Cell Memory Is Regulated by IL-12
Pearce, E. L., & Shen, H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.4.2074 · Cited by 228
“This proliferative process is critical for maturation of TM precursors into fully differentiated TM cells and their long-term maintenance (2, 4, 5, 9, 31).”
BackgroundDifferential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival
Hand, T. W., Cui, W., Jung, Y. W., Sefik, E., Joshi, N. S., Chandele, A., Liu, Y., & Kaech, S. M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003457107 · Cited by 232
Self-citationSlütter, B., Pewe, L. L., Kaech, S. M., & Harty, J. T. (2013) · Immunity · doi:10.1016/j.immuni.2013.09.013 · Cited by 228
“C57BL/6 Tbx21 / P14mice have been described previously (Kaech et al., 2003).”
Self-citationGlucocorticoids in T cell development, differentiation and function
Taves, M. D., & Ashwell, J. D. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-00464-0 · Cited by 246
Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis
Wojciechowski, S., Tripathi, P., Bourdeau, T., Acero, L. F., Grimes, H. L., Katz, J. D., Finkelman, F. D., & Hildeman, D. A. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070618 · Cited by 227
Peripheral Tolerance of CD8 T Lymphocytes
Redmond, W. L., & Sherman, L. A. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.010 · Cited by 234
Jadhav, R. R., Im, S. J., Hu, B., Hashimoto, M., Li, P., Lin, J., Leonard, W. J., Greenleaf, W. J., Ahmed, R., & Goronzy, J. J. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903520116 · Cited by 224
“These cells will be referred to as d8 TE and d8 MP. Previous studies have shown that most of the day 8 TE cells die whereas the day 8 MP cells survive and give rise to the pool of long-lived memory CD8 T cells (37 – 40).”
Self-citationKurd, N. S., He, Z., Louis, T. L., Milner, J. J., Omilusik, K. D., Jin, W., Tsai, M. S., Widjaja, C. E., Kanbar, J. N., Olvera, J. G., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aaz6894 · Cited by 219
Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection.
Lopes, A., Kellam, P., Das, A., Dunn, C., Kwan, A., Turner, J., Peppa, D., Gilson, R., Gehring, A., Bertoletti, A., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33402 · Cited by 227
The Transcription Factor Foxo1 Controls Central-Memory CD8+ T Cell Responses to Infection
Kim, M. V., Ouyang, W., Liao, W., Zhang, M. Q., & Li, M. O. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.013 · Cited by 218
“IL-7-dependent signaling is essential for the long-termmaintenance of memory T cells (Kaech et al., 2003; Schluns et al., 2000).”
BackgroundOne naive T cell, multiple fates in CD8+ T cell differentiation
Gerlach, C., van Heijst, J. W. J., Swart, E., Sie, D., Armstrong, N. J., Kerkhoven, R. M., Zehn, D., Bevan, M. J., Schepers, K., & Schumacher, T. N. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091175 · Cited by 215
“More recently, it has been suggested that precursors of memory cells can already be identified around the peak of the response by the expression of high CD127 and low KLRG-1 levels (Kaech et al., 2003; Joshi et al., 2007).”
BackgroundMethodI mmunological M emory to V iral I nfections
Welsh, R. M., Selin, L. K., & Szomolanyi‐Tsuda, E. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104527 · Cited by 222
Penaloza‐MacMaster, P., Kamphorst, A. O., Wieland, A., Araki, K., Iyer, S. S., West, E. E., O’Mara, L. A., Yang, S., Konieczny, B. T., Sharpe, A. H., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20132577 · Cited by 211
“CD127 is expressed on naive and memory cells to promote their long-term survival but is down-regulated on exhausted T cells (Kaech et al., 2003; Wherry and Ahmed, 2004).”
BackgroundSelf-citationWilliams, J. B., Horton, B. L., Zheng, Y., Duan, Y., Powell, J. D., & Gajewski, T. F. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160485 · Cited by 213
“393JEM Vol. 214, No. 2 To examine functional restoration of the TIL, we sorted the KLRG-1loIL-7Rαlo and KLRG-1hiIL-7Rαlo CD8+ TIL populations from B16.”
BackgroundA guide to adaptive immune memory
Lam, N., Lee, Y. S., & Färber, D. L. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01040-6 · Cited by 236
“Other survival factors for memory cell generation that were first characterized in CD8 + T cells include CD27, the anti-apoptotic protein BCL2, and lack of expression of the killer cell lectin-like receptor G1 (KLRG1) 112–114 .”
Programming for CD8 T Cell Memory Development Requires IL-12 or Type I IFN
Xiao, Z., Casey, K. A., Jameson, S. C., Curtsinger, J., & Mescher, M. F. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803484 · Cited by 213
“The high-affinity IL-7R chain, IL-7R , is down-regulated upon stimulation of naive cells and is expressed on a variable fraction of effector cells (20, 28).”
BackgroundRegulation of Effector and Memory CD8 T Cell Differentiation by IL-2—A Balancing Act
Kalia, V., & Sarkar, S. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02987 · Cited by 217
The Common Cytokine Receptor γ Chain Family of CytokinesPreprint
Lin, J., & Leonard, W. J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028449 · Cited by 215
“IL-7 also regulates the homeostasis of memory CD8+ T cells after viral infection (Kaech et al. 2003), whereas IL-2 can suppress the homeostasis and function of memory CD8+ T cells by Treg cells (Ku et al. 2000; Murakami et al. 2002; Waldmann 2006).”
BackgroundPerales, M., Goldberg, J. D., Yuan, J. D., Koehne, G., Lechner, L., Papadopoulos, E. B., Young, J. W., Jakubowski, A. A., Zaidi, B., Gallardo, H. F., et al. (2012) · Blood · doi:10.1182/blood-2012-06-437236 · Cited by 213
“The ages of the other 2 patients with detectable TRECs were 43 years (14-205) and 54 years (14-204).”
BackgroundChimeric antigen receptor T cell persistence and memory cell formation
McLellan, A. D., & Rad, S. M. A. H. (2019) · Immunology and Cell Biology · doi:10.1111/imcb.12254 · Cited by 211
“This study is in line with the finding that TE with high-level common-c-chain receptor expression are possible precursors of memory T cells, with enhanced persistence through Bcl-2 expression.(23,25) In a macaque model, Berger et al.”
ResultNeidleman, J., Luo, X., Frouard, J., Xie, G., Gill, G., Stein, E. S., McGregor, M., Ma, T., George, A. F., Kosters, A., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100081 · Cited by 188
“Signaling by IL-7 is involved in many key aspects of T cell survival and proliferation and acts by inducing JAK/STAT signaling, which results in increased expression of the Bcl2 anti-apoptotic gene family.(28,47) Consistent with the notion of persisting CD127-expressing SARS-CoV-2-specific T cells is our observation t…”
BackgroundPlasticity in programming of effector and memory CD8+ T‐cell formation
Arens, R., & Schoenberger, S. P. (2010) · Immunological Reviews · doi:10.1111/j.0105-2896.2010.00899.x · Cited by 213
The role of programming in memory T-cell development
Masopust, D., Kaech, S. M., Wherry, E. J., & Ahmed, R. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.02.005 · Cited by 205
Self-citationTissue‐resident memory T cells
Shin, H., & Iwasaki, A. (2013) · Immunological Reviews · doi:10.1111/imr.12087 · Cited by 215
The precursors of memory: models and controversies
Ahmed, R., Bevan, M. J., Reiner, S. L., & Fearon, D. T. (2009) · Nature reviews. Immunology · doi:10.1038/nri2619 · Cited by 207
“Considerable progress has been made on answering this question during the past several year”
BackgroundSelf-citationImmunological memory: lessons from the past and a look to the future
Farber, D. L., Netea, M. G., Radbruch, A., Rajewsky, K., & Zinkernagel, R. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.13 · Cited by 200
Stromnes, I. M., Schmitt, T. M., Hulbert, A., Brockenbrough, J. S., Nguyen, H., Cuevas, C. M., Dotson, A., Tan, X., Hotes, J. L., Greenberg, P. D., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.09.022 · Cited by 201
“Nevertheless, TCR1045 T cell numbers decreased 6-fold in the spleen, but 18-fold in PDA between 8 and 28 days (Figure 4C), revealing a selective disadvantage for T cell survival in the tumor and consistent with the short-lived fate of differentiated effector T cells (Berger et al., 2008; Kaech et al., 2003).”
BackgroundObar, J. J., Molloy, M. J., Jellison, E. R., Stoklasek, T. A., Zhang, W., Usherwood, E. J., & Lefrançois, L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909945107 · Cited by 206
“Originally, memoryprecursors were identified by their retention of CD127 expression (37, 38), which has now been refined to use KLRG1 and CD127 expression to identify MPEC and SLEC (12–14), and, in this report, EEC.”
Method
Metadata
- 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
- Venue
- Nature Immunology
- Published
- 2003-11-16
- Volume
- 4
- Issue
- 12
- Pages
- 1191-1198
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- 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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