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Lineage relationship and protective immunity of memory CD8 T cell subsets
Abstract
Memory CD8 T cells can be divided into two subsets, central (T(CM)) and effector (T(EM)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T(CM) have a greater capacity than T(EM) to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. We also demonstrate that, following antigen clearance, T(EM) convert to T(CM) and that the duration of this differentiation is programmed within the first week after immunization. We propose that T(CM) and T(EM) do not necessarily represent distinct subsets, but are part of a continuum in a linear naive --> effector --> T(EM) --> T(CM) differentiation pathway.
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“the central memory (CM) or effector memory (EM) differentiation states of CD4+ and CD8+ T cells have implications for durability, recirculation, tissue access, and responses upon antigen re-exposure (Kaech et al., 2002; Martin and Badovinac, 2018; Wherry et al., 2003).”
From Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination (2021) · cites this paper as Wherry et al., 2003
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Cites
Dendritic cells and the control of immunity
Banchereau, J., & Steinman, R. M. (1998) · Nature · doi:10.1038/32588 · Cited by 14,486
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846
Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Suresh, M., Altman, J. D., & Ahmed, R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2205 · Cited by 1,978
Self-citationPreferential Localization of Effector Memory Cells in Nonlymphoid Tissue
Masopust, D., Vezys, V., Marzo, A. L., & Lefrançois, L. (2001) · Science · doi:10.1126/science.1058867 · Cited by 1,952
Self-citationCounting 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-citationImmunological memory and protective immunity: understanding their relation
Ahmed, R., & Gray, D. (1996) · Science · doi:10.1126/science.272.5258.54 · Cited by 1,775
Self-citationInterleukin-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
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-citationMoskophidis, D., Lechner, F., Pircher, H., & Zinkernagel, R. M. (1993) · Nature · doi:10.1038/362758a0 · Cited by 1,240
Induction of Bystander T Cell Proliferation by Viruses and Type I Interferon in Vivo
Tough, D. F., Borrow, P., & Sprent, J. (1996) · Science · doi:10.1126/science.272.5270.1947 · Cited by 1,081
Molecular 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
Self-citationVisualizing the generation of memory CD4 T cells in the whole body
Reinhardt, R. L., Khoruts, A., Merica, R., Zell, T., & Jenkins, M. K. (2001) · Nature · doi:10.1038/35065111 · Cited by 1,026
Migueles, S. A., Laborico, A. C., Shupert, W. L., Sabbaghian, M. S., Rabin, R. L., Hallahan, C. W., van Baarle, D., Kostense, S., Miedema, F. F., McLaughlin, M. E., et al. (2002) · Nature Immunology · doi:10.1038/ni845 · Cited by 1,004
Skewed maturation of memory HIV-specific CD8 T lymphocytes
Champagne, P., Ogg, G. S., King, A. S., Knabenhans, C., Ellefsen, K., Nobile, M., Appay, V., Rizzardi, G. P., Fleury, S., Lipp, M., et al. (2001) · Nature · doi:10.1038/35065118 · Cited by 1,002
Differential Requirements for Survival and Proliferation of CD8 Naïve or Memory T Cells
Tanchot, C., Lemonnier, F. A., Pérarnau, B., Freitas, A. A., & Rocha, B. (1997) · Science · doi:10.1126/science.276.5321.2057 · Cited by 856
van Stipdonk, M. J. B., Lemmens, E. E., & Schoenberger, S. P. (2001) · Nature Immunology · doi:10.1038/87730 · Cited by 843
Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice
Arbonés, M. L., Ord, D. C., Ley, K. F., Ratech, H., Maynard-Curry, C., Otten, G., Capon, D. J., & Teddert, T. F. (1994) · Immunity · doi:10.1016/1074-7613(94)90076-0 · Cited by 831
Control of Homeostasis of CD8 + Memory T Cells by Opposing Cytokines
Ku, C., Murakami, M., Sakamoto, A., Kappler, J. W., & Marrack, P. (2000) · Science · doi:10.1126/science.288.5466.675 · Cited by 814
Tan, J. T., Ernst, B., Kieper, W. C., LeRoy, E., Sprent, J., & Surh, C. D. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020066 · Cited by 790
Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice
Murali‐Krishna, K., Lau, L. L., Sambhara, S. R., Lemonnier, F. A., Altman, J. D., & Ahmed, R. (1999) · Science · doi:10.1126/science.286.5443.1377 · Cited by 718
Self-citationChemokines and the Tissue-Specific Migration of Lymphocytes
Kunkel, E. J., & Butcher, E. C. (2002) · Immunity · doi:10.1016/s1074-7613(01)00261-8 · Cited by 688
Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells
Becker, T. C., Wherry, E. J., Boone, D. L., Murali‐Krishna, K., Antia, R., Ma, A. I., & Ahmed, R. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020369 · Cited by 685
Self-citationCytotoxic T-cell memory without antigen
Lau, L. L., Jamieson, B. D., Somasundaram, T., & Ahmed, R. (1994) · Nature · doi:10.1038/369648a0 · Cited by 657
Self-citationMaintaining the norm: T-cell homeostasis
Jameson, S. C. (2002) · Nature reviews. Immunology · doi:10.1038/nri853 · Cited by 597
Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells
Goldrath, A. W., Sivakumar, P. V., Glaccum, M. B., Kennedy, M. K., Bevan, M. J., Benoist, C. O., Mathis, D. J., & Butz, E. A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020033 · Cited by 588
Schluns, K. S., Williams, K., Ma, A. I., Zheng, X. X., & Lefrançois, L. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.10.4827 · Cited by 521
Migratory properties of naive, effector, and memory CD8(+) T cells
Weninger, W., Crowley, M. A., Manjunath, N., & von Andrian, U. H. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.7.953 · Cited by 515
Coordinate Regulation of Complex T Cell Populations Responding to Bacterial Infection
Busch, D. H., Pilip, I. M., Vijh, S., & Pamer, E. G. (1998) · Immunity · doi:10.1016/s1074-7613(00)80540-3 · Cited by 508
Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes.
Manjunath, N., Shankar, P., Wan, J., Weninger, W., Crowley, M., Hieshima, K., Springer, T., Fan, X., Shen, H., Lieberman, J., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13296 · Cited by 507
Class II-Independent Generation of CD4 Memory T Cells from Effectors
Swain, S. L., Hu, H., & Huston, G. E. (1999) · Science · doi:10.1126/science.286.5443.1381 · Cited by 416
Linear Differentiation of Cytotoxic Effectors into Memory T Lymphocytes
Opferman, J. T., Ober, B. T., & Ashton‐Rickardt, P. G. (1999) · Science · doi:10.1126/science.283.5408.1745 · Cited by 380
Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo
Norbury, C. C., Malide, D. A., Gibbs, J. S., Bennink, J. R., & Yewdell, J. W. (2002) · Nature Immunology · doi:10.1038/ni762 · Cited by 339
CCR7 Expression and Memory T Cell Diversity in Humans
Campbell, J. J., Murphy, K. E., Kunkel, E. J., Brightling, C. E., Soler, D., Shen, Z., Boisvert, J., Greenberg, H. B., Vierra, M. A., Goodman, S. B., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.877 · Cited by 335
Modelling T-cell memory by genetic marking of memory T cells in vivo
Jacob, J., & Baltimore, D. (1999) · Nature · doi:10.1038/21208 · Cited by 308
Generation and maintenance of memory CD4+ T Cells
van Leeuwen, E. M. M., Sprent, J., & Surh, C. D. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.02.005 · Cited by 300
Priming of Memory But Not Effector CD8 T Cells by a Killed Bacterial Vaccine
Lauvau, G. S., Vijh, S., Kong, P. L., Horng, T., Kerksiek, K. M., Serbina, N. V., Tuma, R. A., & Pamer, E. G. (2001) · Science · doi:10.1126/science.1064571 · Cited by 285
Kieper, W. C., Tan, J. T., Bondi-Boyd, B., Gapin, L., Sprent, J., Ceredig, R. H., & Surh, C. D. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020067 · Cited by 285
Cutting Edge: Antigen-Independent CD8 T Cell Proliferation
Wong, P., & Pamer, E. G. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.10.5864 · Cited by 269
Arrested differentiation, the self-renewing memory lymphocyte, and vaccination
Fearon, D. T., Manders, P., & Wagner, S. D. (2001) · Science · doi:10.1126/science.1062589 · Cited by 265
Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype
Tomiyama, H., Matsuda, T., & Takiguchi, M. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5538 · Cited by 220
Hislop, A. D., Gudgeon, N. H., Callan, M. F. C., Fazou, C., Hasegawa, H., Salmon, M., & Rickinson, A. B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.4.2019 · Cited by 218
Wills, M. R., Okecha, G., Weekes, M. P., Gandhi, M. K., Sissons, P., & Carmichael, A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5455 · Cited by 208
Harrington, L. E., der Most, R. G. V., Whitton, J. L., & Ahmed, R. (2002) · Journal of Virology · doi:10.1128/jvi.76.7.3329-3337.2002 · Cited by 201
Self-citationHarrington, L. E., Galvan, M., Baum, L. G., Altman, J. D., & Ahmed, R. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.191.7.1241 · Cited by 198
Self-citationCutting Edge: CCR7+ and CCR7− Memory T Cells Do Not Differ in Immediate Effector Cell Function
Unsoeld, H., Krautwald, S., Voehringer, D., Kunzendorf, U., & Pircher, H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.2.638 · Cited by 190
Mueller, S. N., Jones, C. M., Smith, C. M., Heath, W. R., & Carbone, F. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012023 · Cited by 188
Generation and maintenance of memory T cells
Sprent, J., & Surh, C. D. (2001) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00211-9 · Cited by 182
Entry of naive CD4 T cells into peripheral lymph nodes requires L-selectin.
Bradley, L. M., Watson, S. R., & Swain, S. L. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.6.2401 · Cited by 178
Migration and Function of Antigen-Primed Nonpolarized T Lymphocytes in Vivo
Iezzi, G., Scheidegger, D., & Lanzavecchia, A. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.8.987 · Cited by 173
Exploring pathways for memory T cell generation
Sallusto, F., & Lanzavecchia, A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14005 · Cited by 107
Ostler, T., Hussell, T., Surh, C. D., Openshaw, P., & Ehl, S. R. (2001) · European Journal of Immunology · doi:10.1002/1521-4141(200109)31:9 · Cited by 96
Functional Flexibility in T Cells
Laouar, Y., & Crispe, I. N. (2000) · Immunity · doi:10.1016/s1074-7613(00)00029-7 · Cited by 94
Razvi, E. S., Welsh, R. M., & McFarland, H. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.154.2.620 · Cited by 80
Epstein-Barr virus-dependent lymphoproliferative disease: critical role of IL-6
(2000) · Pure Amsterdam UMC · doi:10.1002/1521-4141(200007)30:7 · Cited by 1
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Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062
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Metadata
- Authors
- Wherry, E. J., Teichgräber, V., Becker, T. C., Masopust, D., Kaech, S. M., Antia, R., von Andrian, U. H., & Ahmed, R.
- Affiliations
- Emory University (US)
- Corresponding author
- Ahmed, Rafi
- Venue
- Nature Immunology
- Published
- 2003-02-03
- Volume
- 4
- Issue
- 3
- Pages
- 225-234
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2029128444
- Cited by
- 1,864
- References
- 57
- Citations by year
- 2026: 27 · 2025: 44 · 2024: 47 · 2023: 55 · 2022: 61 · 2021: 65 · 2020: 59 · 2019: 59 · 2018: 54 · 2017: 60 · 2016: 68 · 2015: 50 · 2014: 74 · 2013: 92 · 2012: 84
- FWCI
- 47.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM008169)
- National Institute of Allergy and Infectious Diseases (AI44644, AI 30048)
- 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
- memory CD8+ T cells, central memory T cells, effector memory T cells, T cell lineage, T cell differentiation, T cell proliferation, protective immunity, antigen clearance, naive T cells, T cell persistence
- MeSH terms
- Animals, Cell Communication, Cell Division, Immunologic Memory, Listeriosis, Listeria monocytogenes, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Transgenic, CD8-Positive T-Lymphocytes, Cell Lineage, Mice
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