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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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Counting Antigen-Specific CD8 T Cells: A Reevaluation of Bystander Activation during Viral Infection
Murali‐Krishna, K., Altman, J. D., Suresh, M., Sourdive, D. J. D., Zajac, A. J., Miller, J. D., Slansky, J. E., & Ahmed, R. (1998) · Immunity · doi:10.1016/s1074-7613(00)80470-7 · Cited by 1,918
Self-citationEffector and memory T-cell differentiation: implications for vaccine development
Kaech, S. M., Wherry, E. J., & Ahmed, R. (2002) · Nature Reviews Immunology · doi:10.1038/nri778 · Cited by 1,865
Self-citationLineage relationship and protective immunity of memory CD8 T cell subsets
Wherry, E. J., Teichgräber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., von Andrian, U. H., & Ahmed, R. (2003) · Nature Immunology · doi:10.1038/ni889 · Cited by 1,864
Self-citationLymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine
von Freeden-Jeffry, U., Vieira, P., Lucian, L., McNeil, T., Burdach, S. E. G., & Murray, R. (1995) · Journal of Experimental Medicine · doi:10.1084/jem.181.4.1519 · Cited by 1,648
Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo
Schluns, K. S., Kieper, W. C., Jameson, S. C., & Lefrançois, L. (2000) · Nature Immunology · doi:10.1038/80868 · Cited by 1,619
Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections
Appay, V., Dunbar, P. R., Callan, M. F. C., Klenerman, P., Gillespie, G. M. A., Papagno, L., Ogg, G. S., King, A., Lechner, F., Spina, C. A., et al. (2002) · Nature Medicine · doi:10.1038/nm0402-379 · Cited by 1,556
Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.
Peschon, J. J., Morrissey, P., Grabstein, K. H., Ramsdell, F. J., Maraskovsky, E., Gliniak, B., Park, L. S., Ziegler, S. F., Williams, D. E., Ware, C. B., et al. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.5.1955 · Cited by 1,553
Phenotypic and functional separation of memory and effector human CD8+ T cells
Hamann, D., Baars, P. A., Rep, M. H. G., Hooibrink, B., Kerkhof-Garde, S. R., Klein, M. R., & Lier, R. A. W. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.9.1407 · Cited by 1,366
Kaech, S. M., & Ahmed, R. (2001) · Nature Immunology · doi:10.1038/87720 · Cited by 1,265
Self-citationMolecular and functional profiling of memory CD8 T cell differentiation.
Kaech, S., Hemby, S., Kersh, E., & Ahmed, R. (2002) · Cell · doi:10.1016/s0092-8674(02)01139-x · Cited by 1,081
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Armed and Ready: Transcriptional Regulation of Tissue-Resident Memory CD8 T Cells
Behr, F. M., Chuwonpad, A., Stark, R., & van Gisbergen, K. P. J. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01770 · Cited by 124
“In contrast, memory precursors express very low amounts of KLRG1, but maintain expression of IL-7Rα (CD127) (51).”
BackgroundAraki, K., Ellebedy, A. H., & Ahmed, R. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.08.006 · Cited by 134
Self-citationRequirements for CD8 T-cell priming, memory generation and maintenance
Prlic, M., Williams, M. A., & Bevan, M. J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.010 · Cited by 135
BACH transcription factors in innate and adaptive immunity
Igarashi, K., Kurosaki, T., & Roychoudhuri, R. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.26 · Cited by 132
Price, G. E., Soboleski, M. R., Lo, C.-Y., Misplon, J. A., Pappas, C., Houser, K. V., Tumpey, T. M., & Epstein, S. L. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.08.053 · Cited by 132
Badr, G., Bédard, N., Abdel-Hakeem, M. S., Trautmann, L., Willems, B. E., Villeneuve, J., Haddad, E. K., Sékaly, R., Bruneau, J., & Shoukry, N. H. (2008) · Journal of Virology · doi:10.1128/jvi.01083-08 · Cited by 130
“memory T cells (29), and programmed death receptor-1”
BackgroundResultStrength of Stimulus and Clonal Competition Impact the Rate of Memory CD8 T Cell Differentiation
Sarkar, S., Teichgräber, V., Kalia, V., Polley, A. M., Masopust, D., Harrington, L. E., Ahmed, R., & Wherry, E. J. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6704 · Cited by 128
“The P14 precursor frequency also impacts the rate at which the P14 cells acquire a CD127high phenotype (Fig.”
ResultInfluentialSelf-citationChen, L., & Shen, Z. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0291-4 · Cited by 142
Wilson, D. C., Matthews, S., & Yap, G. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.9.5935 · Cited by 131
“Because the retention of IL-7R expression in a subset of effector cells generated during primary infection has been previously associated with long-term survival (35), their relative immaturity and the high frequency of IL-7R expression in FII suggest that some of these cells might progress to become effector memory T…”
BackgroundApoptosis and the homeostatic control of immune responses
Hildeman, D. A., Jørgensen, T. N., Kappler, J. W., & Marrack, P. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.05.005 · Cited by 131
Liu, X., Li, J., Chen, T., Nallaparaju, K. C., Yan, X. S., Tanaka, S., Ichiyama, K., Zhang, X., Zhang, L., Wen, X., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.038 · Cited by 133
IL-2 and Beyond in Cancer Immunotherapy
Wrangle, J. M., Patterson, A., Johnson, C. B., Neitzke, D. J., Mehrotra, S., Denlinger, C. E., Paulos, C. M., Li, Z., Cole, D. J., & Rubinstein, M. P. (2018) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2017.0101 · Cited by 132
Clonal expansion of innate and adaptive lymphocytes
Adams, N. M., Grassmann, S. A., & Sun, J. C.-Y. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0307-4 · Cited by 129
Increased CD127 expression on activated FOXP3+CD4+ regulatory T cells
Simonetta, F., Chiali, A., Cordier, C., Urrutia, A., Girault, I., Bloquet, S., Tanchot, C., & Bourgeois, C. (2010) · European Journal of Immunology · doi:10.1002/eji.201040531 · Cited by 129
Toll-like Receptors from the Perspective of Cancer Treatment
Javaid, N., & Choi, S. (2020) · Cancers · doi:10.3390/cancers12020297 · Cited by 138
“Increased PKC and PI3K signaling activities cause costimulation of TLR signaling [170,171].”
BackgroundImmune memory redefined: characterizing the longevity of natural killer cells
Sun, J. C.-Y., Beilke, J. N., & Lanier, L. L. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00900.x · Cited by 126
Brien, J. D., Uhrlaub, J. L., & Nikolich‐Žugich, J. (2007) · European Journal of Immunology · doi:10.1002/eji.200737196 · Cited by 128
Lukens, M. V., van de Pol, A. C., Coenjaerts, F. E. J., Jansen, N. J. G., Kamp, V. M., Kimpen, J. L. L., Rossen, J. W. A., Ulfman, L. H., Tacke, C. E. A., Viveen, M. C., et al. (2009) · Journal of Virology · doi:10.1128/jvi.01807-09 · Cited by 133
“CD127 is the receptor for interleukin 7 (IL-7) that is expressed on naïve and memory T cells and is required for homeostatic proliferation (33).”
BackgroundEarly Signals during CD8+ T Cell Priming Regulate the Generation of Central Memory Cells
Obar, J. J., & Lefrançois, L. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000492 · Cited by 123
“Earlier work demonstrated that a population of effector CD8+ T cells retains the expression of CD127 (IL-7Rα) (12,13).”
BackgroundInfluentialKeating, S. M., Bejon, P., Berthoud, T. K., Vuola, J. M., Todryk, S. M., Webster, D. P., Dunachie, S. J., Moorthy, V., McConkey, S. J., Gilbert, S. C., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.5675 · Cited by 126
“The identification of IL-7R high staining cells may be a way of distinguishing cells that will evolve into a memory population; however, with limitations on cell numbers available in a vaccine clinical study, it has proved difficult to isolate the IL-7R high population for further analysis (33).”
BackgroundPapavassiliou, A. G., & Musti, A. M. (2020) · Cells · doi:10.3390/cells9112470 · Cited by 124
Horton, B. L., Morgan, D. M., Momin, N., Zagorulya, M., Torres-Mejia, E., Bhandarkar, V., Wittrup, K. D., Love, J. C., & Spranger, S. (2021) · Science Immunology · doi:10.1126/sciimmunol.abi8800 · Cited by 124
Heidema, J., Lukens, M. V., van Maren, W. W. C., van Dijk, M. E. A., Otten, H. G., van Vught, A. J., van der Werff, D. B. M., van Gestel, S., Semple, M. G., Smyth, R. L., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.12.8410 · Cited by 125
“The RSVspecific T cells initially lost CD127 expression, which they partly regained during convalescence, presumably showing their destiny to become memory cells (31).”
BackgroundLongitudinal Changes in CD4+ T-Cell Memory Responses Induced by BCG Vaccination of Newborns
Soares, A. P., Chung, C. K. C. K., Choice, T., Hughes, E. J., Jacobs, G., van Rensburg, E. J., Khomba, G., de Kock, M., Lerumo, L., Makhethe, L., et al. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jis941 · Cited by 125
“T-Cell Responses to BCG Vaccination • JID 2013:207 (1 April) • 1087 D ow nloaded from https://academ ic.oup.com /jid/article-abstract/207/7/1084/2192451 by guest on 28 D ecem ber 2018 expression up to 27 weeks, when the level of Bcl-2 expression peaked (6 vs 10 weeks [P < .0001]; Figure 2B).”
BackgroundInfluentialHuang, C., Loo, E. X. L., Kuo, I.-C., Soh, G. H., Goh, D. L. M., Lee, B. W., & Chua, K. Y. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100259 · Cited by 124
“IL-7Ra is normally expressed at high levels on naive T cells, and it is rapidly downregulated upon T cell activation (32) and reexpressed by a small fraction of effector T cells destined to survive as memory cells (33).”
BackgroundSTAT5 Is Critical To Maintain Effector CD8+ T Cell Responses
Tripathi, P., Kurtuluş, S., Wojciechowski, S., Sholl, A., Hoebe, K. H. N., Morris, S. C., Finkelman, F. D., Grimes, H. L., & Hildeman, D. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000842 · Cited by 123
“Results Reciprocal expression of CD122 and CD127 on effector CD8 and CD4 T cells Whereas expression of cytokine receptors by effector CD8 T cells is dynamic (22, 23), few studies have examined cytokine receptor expression on activated, non-TCR transgenic CD4 T cells.”
Cutting Edge: Latecomer CD8 T Cells Are Imprinted with a Unique Differentiation Program
D’Souza, W. N., & Hedrick, S. Μ. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.777 · Cited by 122
“The expression of IL-7R (CD127) at the peak of the proliferative phase was shown to identify memory CD8 T cell precursors, and this has been interpreted to indicate that IL-7-mediated signals are sufficient to allow this small subset of effector cells to survive and differentiate into memory cells (23, 24).”
BackgroundCD4−CD8− T cells control intracellular bacterial infections both in vitro and in vivo
Cowley, S. C., Hamilton, E., Frelinger, J. A., Su, J., Forman, J., & Elkins, K. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050569 · Cited by 122
“In particular, recent experiments indicate an important role for IL-7 in T cell survival, promoting long-term persistence of both naive and memory T cells through the regulation of apoptosis (27).”
BackgroundDunham, R. M., Cervasi, B., Brenchley, J. M., Albrecht, H., Weintrob, A., Sumpter, B., Engram, J. C., Gordon, S. N., Klatt, N. R., Frank, I., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5582 · Cited by 121
Quigley, M. M., Martinez, J., Huang, X., & Yang, Y. (2008) · Blood · doi:10.1182/blood-2008-03-148809 · Cited by 121
Kim, C., Hu, B., Jadhav, R. R., Jin, J., Zhang, H., Cavanagh, M., Akondy, R. S., Ahmed, R., Weyand, C. M., & Goronzy, J. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.074 · Cited by 124
Self-citationCD4+ memory T cells: functional differentiation and homeostasis
Stockinger, B., Bourgeois, C., & Kassiotis, G. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00381.x · Cited by 121
“and could therefore be termed precursors of memory T cells has been demonstrated (37).”
BackgroundDendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation.
Stonier, S. W., Ma, L. J., Castillo, E. F., & Schluns, K. (2008) · Blood · doi:10.1182/blood-2008-05-156307 · Cited by 133
Cui, W., Joshi, N. S., Jiang, A., & Kaech, S. M. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.01.088 · Cited by 121
“(B) Small numbers of WT, IFNγR1−/− and IL-12Rβ2−/− P14 CD8 T cells were transferred into naïve mice that were then immunized with DC-33+ CpG. P14 CD8 T cells and were analyzed for expression of KLRG1 and IL-7R seven days later.”
InfluentialSelf-citationWu, T., Wieland, A., Araki, K., Davis, C. W., Ye, L., Hale, J. S., & Ahmed, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207327109 · Cited by 120
“We used the P14 TCR transgenic system (TCR specific to DGP33–41 of LCMV) (5) and sorted naïve, day 5 effector, day 8 effector, and memory (day >60) P14 cells.”
MethodSelf-citationSalem, M. L., Kadima, A. N., El-Naggar, S. A., Rubinstein, M. P., Chen, Y., Gillanders, W. E., & Cole, D. J. (2006) · Journal of Immunotherapy · doi:10.1097/01.cji.0000211311.28739.e3 · Cited by 119
Masopust, D., Murali-Krishna, K., & Ahmed, R. (2007) · Journal of Virology · doi:10.1128/jvi.01459-06 · Cited by 114
Self-citationFunctional Dichotomy between OX40 and 4-1BB in Modulating Effector CD8 T Cell Responses
Lee, S., Park, Y., Song, A., Cheroutre, H., Kwon, B. S., & Croft, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4464 · Cited by 120
“OX40 / CD8 cells showed defects in down-regulation of the effector markers CD62L and CD27, the secretion of cytokines, and importantly cytotoxic activity.”
BackgroundResultInfluentialT cell homeostasis: Keeping useful T cells alive and live T cells useful
Jameson, S. C. (2005) · Seminars in Immunology · doi:10.1016/j.smim.2005.02.003 · Cited by 118
Bim mediates apoptosis of CD127lo effector T cells and limits T cell memory
Wojciechowski, S., Jordan, M. B., Zhu, Y., White, J., Zajac, A. J., & Hildeman, D. A. (2006) · European Journal of Immunology · doi:10.1002/eji.200635897 · Cited by 120
Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population
Milner, J. J., Nguyen, H., Omilusik, K. D., Reina‐Campos, M., Tsai, M. S., Toma, C., Delpoux, A., Boland, B. S., Hedrick, S. Μ., Chang, J. T., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2008571117 · Cited by 115
Shi, L. Z., Fu, T., Guan, B., Chen, J., Blando, J. M., Allison, J. P., Xiong, L., Subudhi, S. K., Gao, J., & Sharma, P. (2016) · Nature Communications · doi:10.1038/ncomms12335 · Cited by 111
Dissecting the human immunologic memory for pathogens
Zielinski, C. E., Corti, D., Mele, F., Pinto, D., Lanzavecchia, A., & Sallusto, F. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.01000.x · Cited by 118
van der Waart, A. B., van de Weem, N. M. P., Maas, F., Kramer, C. S. M., Kester, M. G. D., Falkenburg, J. H. F., Schaap, N. P., Jansen, J. H., van der Voort, R., Gattinoni, L., et al. (2014) · Blood · doi:10.1182/blood-2014-05-578583 · Cited by 116
“For instance, it has been shown that T cells expressing higher levels of IL-7Ra survive and proliferate better than IL-7Ra T cells following antigen stimulation in human T cells and in mouse models.(41,42) Importantly, possible self-renewal potential of Akt-inhibited CD8(1) T cells was observed after 3 weeks of in viv…”
BackgroundResident memory T cells are a cellular reservoir for HIV in the cervical mucosa
Cantero-Pérez, J., Grau-Expósito, J., Serra‐Peinado, C., Freire, D. A. R., Luque-Ballesteros, L., Astorga-Gamaza, A., Castellví, J., Sanhueza, T., Tapia, G., Lloveras, B., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12732-2 · Cited by 115
French, R. R., Taraban, V. Y., Crowther, G., Rowley, T. F., Gray, J. C., Johnson, P., Tutt, A. L., Al‐Shamkhani, A., & Glennie, M. J. (2007) · Blood · doi:10.1182/blood-2006-11-057216 · Cited by 116
Lichterfeld, M. D., Yu, X. G., Mui, S. K., Williams, K. L., Piechocka‐Trocha, A., Brockman, M. A., Allgaier, R. L., Waring, M. T., Koibuchi, T., Johnston, M. N., et al. (2007) · Journal of Virology · doi:10.1128/jvi.01388-06 · Cited by 116
“We subsequently assessed whether these high-avidity epitopespecific CD8 T-cell clones differed from the persisting loweravidity clones in activation status and expression of the receptor for IL-7, a cytokine that has recently been identified to be responsible for the maintenance of CD8 T cells and their transformation…”
BackgroundDOCK8 is essential for T‐cell survival and the maintenance of CD8+ T‐cell memory
Lambe, T., Crawford, G., Johnson, A. L., Crockford, T. L., Bouriez‐Jones, T., Smyth, A. M., Pham, T. H. M., Zhang, Q., Freeman, A. F., Cyster, J. G., et al. (2011) · European Journal of Immunology · doi:10.1002/eji.201141759 · Cited by 119
IL-7–induced proliferation of recent thymic emigrants requires activation of the PI3K pathway
Swainson, L. A., Kinet, S., Mongellaz, C., Sourisseau, M., Henriques, T., & Taylor, N. N. (2006) · Blood · doi:10.1182/blood-2006-06-027912 · Cited by 127
IL-15 Regulates CD8+ T Cell Contraction during Primary Infection
Yajima, T., Yoshihara, K., Nakazato, K., Kumabe, S., Koyasu, S., Sad, S., Shen, H., Kuwano, H., & Yoshikai, Y. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.1.507 · Cited by 115
“A recent study has shown that only those IL-7R -expressing Ag-specific CD8 T cells at the peak of primary immune response give rise to memory cells after adoptive transfer into naive hosts (29, 30), suggesting that only IL-7R high cells are capable of surviving CD8 T cell contraction.”
BackgroundBlimp‐1 homolog Hobit identifies effector‐type lymphocytes in humans
Braga, F. A. V., Hertoghs, K. M. L., Kragten, N. A. M., Doody, G. M., Barnes, N. A., Remmerswaal, E. B. M., Hsiao, C., Moerland, P. D., Wouters, D., Derks, I. A. M., et al. (2015) · European Journal of Immunology · doi:10.1002/eji.201545650 · Cited by 114
Popescu, I., Mannem, H. C., Winters, S. A., Hoji, A., Silveira, F. P., McNally, E. J., Pipeling, M. R., Lendermon, E. A., Morrell, M. R., Pilewski, J. M., et al. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201805-0825oc · Cited by 116
The descent of memory T-cell subsets
Lefrançois, L., & Marzo, A. L. (2006) · Nature reviews. Immunology · doi:10.1038/nri1866 · Cited by 119
“But during a primary response, how can both lineages be derived from the same pool of effector CD8 + T cells? Recent data indicate that memory CD8 + T-cell 'precursors' can be identified before the contraction phase of the response to acute infectio”
BackgroundThe Emergence and Functional Fitness of Memory CD4+ T Cells Require the Transcription Factor Thpok
Ciucci, T., Vacchio, M. S., Gao, Y., Tomassoni‐Ardori, F., Candia, J., Mehta, M., Zhao, Y., Tran, B. Q., Pepper, M., Tessarollo, L., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.019 · Cited by 111
“We also noted that the GP66-specific Thpok-deficient population included an IL-7Ra KLRG1 component typical of short-lived terminally differentiated effectors (Kaech et al., 2003) (Figure 4A).”
The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy
Wang, C., Kong, L.-Z., Kim, S., Lee, S., Oh, S., Jo, S., Jang, I.-H., & Kim, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810412 · Cited by 119
“Correspondingly, basal levels of IL-7 can also regulate the number of memory CD8 T cells formed [44].”
BackgroundMarziali, M., Santis, W. D., Carello, R., Leti, W., Esposito, A., Isgrò, A., Fimiani, C., Sirianni, M. C., Mezzaroma, I., & Aiuti, F. (2006) · AIDS · doi:10.1097/01.aids.0000247588.69438.fd · Cited by 114
Jung, Y. W., Rutishauser, R. L., Joshi, N. S., Haberman, A. M., & Kaech, S. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001948 · Cited by 111
“It was noted previously that the reduction in KLRG1IL-7R cells occurs primarily as a result of cell death, rather than conversion to a KLRG1 IL-7R phenotype (12, 39).”
BackgroundSelf-citationWang, Y., Misumi, I., Gu, A.-D., Curtis, T. A., Su, L., Whitmire, J. K., & Wan, Y. Y. (2013) · Nature Immunology · doi:10.1038/ni.2623 · Cited by 109
Quinn, K. M., Costa, A. D. S., Yamamoto, A., Berry, D., Lindsay, R. W. B., Darrah, P. A., Wang, L., Cheng, C., Kong, W., Gall, J. G. D., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202861 · Cited by 109
“classification of effector and memory CD8 T cells in mice is based on expression of CD127, the IL-7 receptor a-chain, and KLRG1 (44, 45).”
BackgroundRespiratory Syncytial Virus–Specific CD8 + Memory T Cell Responses in Elderly Persons
de Bree, G. J., Heidema, J., van Leeuwen, E. M. M., van Bleek, G. M., Jonkers, R. E., Jansen, H. M., van Lier, R. A. W., & Out, T. A. (2005) · The Journal of Infectious Diseases · doi:10.1086/429695 · Cited by 108
“Recently, in a murine model of lymphocytic choriomeningitis virus infection, it was found that memory T cells also express interleukin (IL)–7Ra [11].”
BackgroundBengsch, B., Spangenberg, H. C., Kersting, N., Neumann‐Haefelin, C., Panther, E., von Weizsäcker, F., Blum, H. E., Pircher, H., & Thimme, R. (2006) · Journal of Virology · doi:10.1128/jvi.01354-06 · Cited by 109
“have shown in the mouse model of LCMV infection that only a fraction (9 to 15%) of antigenspecific CD8 T cells are CD127 during acute infection, but after viral clearance, CD127 CD8 T cells preferentially survive and dominate the memory pool (17).”
BackgroundPotential roles for CD8+ T cells in rheumatoid arthritis
Carvalheiro, H., da Silva, J. A. P., & Souto‐Carneiro, M. (2012) · Autoimmunity Reviews · doi:10.1016/j.autrev.2012.07.011 · Cited by 108
“This is based in the presence or absence of co-stimulatory (CD27, CD28, CD45RA) and adhesion (CD62L)molecules and the chemokine receptor CCR7 [27].”
BackgroundThe Role of Thymic Stromal Lymphopoietin in CD8+ T Cell Homeostasis
Rochman, Y., & Leonard, W. J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.11.7699 · Cited by 108
“Interestingly, in contrast to the down-regulation of IL-7R expression on activated CD8 T cells (19, 26), TCR activation instead increased TSLPR expression (Fig.”
ResultManipulating the Rate of Memory CD8+ T Cell Generation after Acute Infection
Badovinac, V. P., & Harty, J. T. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.1.53 · Cited by 107
“Recently, it has been suggested that effector CD8 T cells express high levels of inhibitory KLRG-1, and low levels of IL-7R (CD127) represent apoptosis-susceptible and terminally differentiated or senescent effector cells (19).”
BackgroundReduced generation of lung tissue–resident memory T cells during infancy
Zens, K. D., Chen, J. K., Guyer, R. S., Wu, F. L., Cvetkovski, F., Miron, M., & Färber, D. L. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170521 · Cited by 101
“…No. 10 Mechanisms for altered infant respiratory immunity | Zens et al.2924 receptor, a well-described T cell survival factor (Schluns et al., 2000; Kaech et al., 2003), with high levels of T-bet driving the generation of terminally differentiated, short-lived effector cells (Intlekofer et al.,…”
BackgroundStem, Effector, and Hybrid States of Memory CD8+ T Cells
Lugli, E., Galletti, G., Boi, S. K., & Youngblood, B. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.11.004 · Cited by 107
Du, X., Tang, Y., Xu, H., Lit, L., Walker, W. L., Ashwood, P., Gregg, J. P., & Sharp, F. R. (2006) · Genomics · doi:10.1016/j.ygeno.2006.02.003 · Cited by 107
Safety and Immunogenicity of Tyrosinase DNA Vaccines in Patients with Melanoma
Wolchok, J. D., Yuan, J. D., Houghton, A. N., Gallardo, H. F., Rasalan, T. S., Wang, J., Zhang, Y., Ranganathan, R., Chapman, P. B., Krown, S. E., et al. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300290 · Cited by 107
Pinto, A. K., Daffis, S., Brien, J. D., Gainey, M. D., Yokoyama, W. M., Sheehan, K. C. F., MURPHY, K. M. M., Schreiber, R. D., & Diamond, M. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002407 · Cited by 107
“These markers are significant because in mice activated, lytic CD8 T cells display a CD44 CD43 CD127 granzyme B phenotype whereas memory CD8 T cells express a CD44 CD43 CD127 granzyme B phenotype [53-55].”
BackgroundKaufman, D., Liu, J.-Y., Carville, A., Mansfield, K., Havenga, M., Goudsmit, J., & Barouch, D. (2008) · Journal of Immunology · doi:10.4049/jimmunol.181.6.4188 · Cited by 72
Zebley, C. C., Brown, C., Tian, M., Fan, Y., Alli, S., Boi, S. K., Galletti, G., Lugli, E., Langfitt, D. M., Métais, J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.110079 · Cited by 109
“Following antigen clearance, a subset of effector cells further develops into long-lived quiescent memory T cells that retain a multipotent epigenetic program in addition to the effector-associated epigenetic imprints, which enable recall of effector functions upon antigen reencounter (Kaech et al., 2003; Wherry et al…”
BackgroundMemory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes
Narni-Mancinelli, É., Campisi, L., Bassand, D., Cazareth, J., Gounon, P., Glaichenhaus, N., & Lauvau, G. S. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070204 · Cited by 106
Exploring regulatory mechanisms of CD8 + T cell contraction
Prlic, M., & Bevan, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808997105 · Cited by 110
“The second hypothesis is based on the observation that the IL7R hi KLRG-1lo (memory precursor cell) effector cell subset present at the peak of expansion preferentially survives contraction, whereas the IL7R lo KLRG-1hi (terminally differentiated effector cell) subset is more prone to cell death (18).”
BackgroundAcquired and natural memory T cells join forces at the mucosal front line
Cheroutre, H., & Madakamutil, L. T. (2004) · Nature reviews. Immunology · doi:10.1038/nri1333 · Cited by 106
“These primary activated T cells control the initial antigen challenge and subsequently die, although a subset differentiate into long-term memory T cell”
Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
Osborne, L. C., Dhanji, S., Snow, J. W., Priatel, J. J., Ma, M. C., Miners, M. J., Teh, H., Goldsmith, M. A., & Abraham, N. B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061871 · Cited by 107
Regulating the immune system via IL-15 transpresentation
Castillo, E. F., & Schluns, K. S. (2012) · Cytokine · doi:10.1016/j.cyto.2012.06.017 · Cited by 105
“effectors as IL-7 also has a role [63–65].”
BackgroundT-cell death and cancer immune tolerance
Lu, B., & Finn, O. J. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402274 · Cited by 106
“These IL-7r-positive effector T cells were shown to be the precursors of memory cells.(106)”
BackgroundLacombe, M.-H., Hardy, M., Rooney, J., & Labrecque, N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4400 · Cited by 102
“(16), more effector V 5LTAOC / CD8 T cells main-”
BackgroundResultInfluentialProspects for an influenza vaccine that induces cross‐protective cytotoxic T lymphocytes
Brown, L. E., & Kelso, A. (2009) · Immunology and Cell Biology · doi:10.1038/icb.2009.16 · Cited by 103
Okoye, I., Houghton, M., Tyrrell, D. L., Barakat, K., & Elahi, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01215 · Cited by 105
“Expression of CD127 by effector CD8+ T cells is used to identify memory precursor cells and antigen-independent memory T cells that mediate protective immunity (80).”
BackgroundThe CD4-centered universe of human T cell subsets
Geginat, J., Paroni, M., Facciotti, F., Gruarin, P., Kastirr, I., Caprioli, F., Pagani, M., & Abrignani, S. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.012 · Cited by 112
T-Cell Immunophenotyping Distinguishes Active From Latent Tuberculosis
Pollock, K. M., Whitworth, H. S., Montamat‐Sicotte, D., Grass, L., Cooke, G., Kapembwa, M. S., Kon, O. M., Sampson, R. D., Taylor, G. P., & Lalvani, A. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit265 · Cited by 105
“of differentiated murine T effector cells distinct from effector memory cells [18, 19].”
BackgroundRadziewicz, H., Ibegbu, C., Hon, H., Osborn, M. K., Obideen, K. M., Wehbi, M. A., Freeman, G. J., Lennox, J. L., Workowski, K., Hanson, H. L., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01075-08 · Cited by 102
“Since upregulation of CD127 has been linked to formation of functional memory T cells (25, 28), we hypothesize that these CD127 HCV-specific CD8 T cells seen during early, acute HCV infection represent a population of either effector cells with memory T-cell potential or a population of bona fide memory T cells.”
BackgroundBmi1 regulates memory CD4 T cell survival via repression of the Noxa gene
Yamashita, M., Kuwahara, M., Suzuki, A., Hirahara, K., Shinnaksu, R., Hosokawa, H., Hasegawa, A., Motohashi, S., Iwama, A., & Nakayama, T. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072000 · Cited by 105
Bcl-2 Allows Effector and Memory CD8+ T Cells To Tolerate Higher Expression of Bim
Kurtuluş, S., Tripathi, P., Moreno‐Fernandez, M. E., Sholl, A., Katz, J. D., Grimes, H. L., & Hildeman, D. A. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100102 · Cited by 102
“More recently, it was found that subsets of effector T cells differ in their expression of Bcl-2 (13, 33).”
BackgroundBejon, P., Mwacharo, J. K., Kai, O. K., Todryk, S. M., Keating, S. M., Lowe, B. S., Lang, T. A., Mwangi, T., Gilbert, S. C., Peshu, N. M., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4193 · Cited by 102
“The priming of T cells responses depends on dendritic cells, whereas subsequent memory appears to be independent of dendritic cells (34), but is dependent on cytokines such as IL-7 and IL-15 (35, 36).”
BackgroundMemory T-Cell Heterogeneity and TerminologyPreprint
Muroyama, Y., & Wherry, E. J. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a037929 · Cited by 104
Self-citationKLRG1+ Memory CD8 T Cells Combine Properties of Short-Lived Effectors and Long-Lived Memory
Renkema, K. R., Huggins, M. A., da Silva, H. B., Knutson, T. P., Henzler, C. M., & Hamilton, S. E. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1901512 · Cited by 102
Heit, A., Schmitz, F., O’Keeffe, M. A., Staib, C., Busch, D. H., Wagner, H., & Huster, K. M. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.7.4373 · Cited by 101
Perales, M., Yuan, J. D., Powel, S., Gallardo, H. F., Rasalan, T. S., Gonzalez, C., Manukian, G., Wang, J., Zhang, Y., Chapman, P. B., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.196 · Cited by 101
Gray, S. M., Kaech, S. M., & Staron, M. M. (2014) · Immunological Reviews · doi:10.1111/imr.12205 · Cited by 105
“Building on the seminal work of Schluns et al. (17) demonstrating the importance of IL-7 and IL-7R expression on CTLs for the homeostasis and survival of memory CTLs, Kaech et al.(18) went on to show how IL-7Rhi CTLs at the peak of the effector response were the direct precursors of central memory CD8+ T cells that ar…”
BackgroundSelf-citationRocha, B., & Tanchot, C. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.03.004 · Cited by 101
Chung, H. K., McDonald, B., & Kaech, S. M. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20201730 · Cited by 105
Self-citationClonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection
Dillen, C. A., Pinsker, B. L., Marusina, A. I., Merleev, A. A., Farber, O. N., Liu, H., Archer, N. K., Lee, D. B., Wang, Y., Ortines, R. V., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96481 · Cited by 102
Tumor Microenvironment and Immune Escape
Ferrone, S., & Whiteside, T. L. (2007) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2007.08.004 · Cited by 99
Modulating T‐cell homeostasis with IL‐7: preclinical and clinical studies
Capitini, C. M., Chisti, A. A., & Mackall, C. L. (2009) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2009.02085.x · Cited by 98
Ruby, C. E., Redmond, W. L., Haley, D. P., & Weinberg, A. D. (2006) · European Journal of Immunology · doi:10.1002/eji.200636428 · Cited by 98
Koesters, S. A., Alimonti, J. B., Wachihi, C., Matu, L., Anzala, O. A., Kimani, J., Embree, J. E., Plummer, F. A., & Fowke, K. R. (2006) · European Journal of Immunology · doi:10.1002/eji.200535111 · Cited by 96
Homeostatic maintenance of T cells and natural killer cells
Boyman, O., Krieg, C., Homann, D., & Sprent, J. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0968-7 · Cited by 99
Hobit identifies tissue-resident memory T cell precursors that are regulated by Eomes
Vidal, L. P., Behr, F. M., Kragten, N. A. M., Nota, B., Wesselink, T. H., Kavazović, I., Covill, L., Schuller, M. B. P., Bryceson, Y. T., Wensveen, F. M., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abg3533 · Cited by 101
“Expression of the surface molecules KLRG1 and CD127 classifies activated CD8+ T cells into memory precursor effector cells (MPECs; CD127hiKLRG1lo) with the capacity to form memory CD8+ T cells and terminal effector cells (TECs; CD127loKLRG1hi) that lack this capacity (14, 15).”
Background
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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