Memory T Cells Constitute a Subset of the Human CD8+CD45RA+ Pool with Distinct Phenotypic and Migratory Characteristics
Open accessAbstract
Using HLA class I-viral epitope tetramers to monitor herpes virus-specific CD8+ T cell responses in humans, we have shown that a significant fraction of responding cells revert from a CD45RO+ to a CD45RA+ state after priming. All tetramer-binding CD45RA+ cells, regardless of epitope specificity, expressed a phenotype LFA-1highCCR7low that was stable for at least 10 years in infectious mononucleosis patients and indefinitely in asymptomatic carriers. CD8+CD45RA+LFA-1high cells were not present in cord blood but in adults account for up to 50% of CD8+CD45RA+ cells. These CD45RA+LFA-1high cells have significantly shorter telomeres than CD45RA+LFA-1low cells, suggesting that the latter represent a naive population, while the former are memory cells. CD45RA+ memory cells are a stable population of noncycling cells, but on stimulation they are potent producers of IFN-γ, while naive CD8+ cells produce only IL-2. The chemokine receptor profile and migratory potential of CD45RA+ memory cells is very similar to CD45RO+ cells but different to naive CD8 cells. In accord with this, CD45RA+ memory cells were significantly underrepresented in lymph nodes, but account for virtually all CD8+CD45RA+ T cells in peripheral tissues of the same individuals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Since the patients are adults, the increase in naïve CD8+ T-cells over 2 years may suggest thymic-independent recovery or the generation of a stable CD45RA+ memory cell subset from the CD45RO+ pool, also described in patients receiving checkpoint blockade.
“Since the patients are adults, the increase in naïve CD8+ T-cells over 2 years may suggest thymic-independent recovery [39], or the generation of a stable CD45RA+ memory cell subset from the CD45RO+ pool [43], also described in patients receiving checkpoint blockade [24].”
From Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm (2021) · cites this paper as [43]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Phenotypic Analysis of Antigen-Specific T Lymphocytes
Altman, J. D., Moss, P. A. H., Goulder, P. J. R., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., McMichael, A. J., & Davis, M. M. (1996) · Science · doi:10.1126/science.274.5284.94 · Cited by 3,544 · see citing works
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 · see citing works
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 · see citing works
Immunological memory and protective immunity: understanding their relation
Ahmed, R., & Gray, D. (1996) · Science · doi:10.1126/science.272.5258.54 · Cited by 1,775 · cited 2× · see citing works
“Memory cells are believed to recirculate to lymph nodes, where they acquire Ag on subsequent secondary challenge (1).”
BackgroundMacLennan, I. C. M. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.001001 · Cited by 1,728 · see citing works
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 · see citing works
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 · see citing works
Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells.
Akbar, A. N., Terry, L. A., Timms, A., Beverley, P. C. L., & Janossy, G. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.7.2171 · Cited by 921 · see citing works
Self-citationCallan, M. F. C., Tan, L., Annels, N., Ogg, G. S., Wilson, J. D. K., O'Callaghan, C. A., Steven, N., McMichael, A. J., & Rickinson, A. B. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.9.1395 · Cited by 892 · see citing works
Self-citationChemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses
Sallusto, F., Lanzavecchia, A., & Mackay, C. R. (1998) · Immunology Today · doi:10.1016/s0167-5699(98)01346-2 · Cited by 888 · see citing works
HUMAN CYTOTOXIC T LYMPHOCYTE RESPONSES TO EPSTEIN-BARR VIRUS INFECTION
Rickinson, A. B., & Moss, D. J. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.405 · Cited by 759 · see citing works
Self-citationWills, M. R., Carmichael, A. J., Mynard, K., Jin, X., Weekes, M. P., Plachter, B., & Sissons, J. G. P. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.7569-7579.1996 · Cited by 687 · see citing works
Virus-Specific CD8+ T Cells in Primary and Secondary Influenza Pneumonia
Flynn, K. J., Belz, G. T., Altman, J. D., Ahmed, R., Woodland, D. L., & Doherty, P. C. (1998) · Immunity · doi:10.1016/s1074-7613(00)80573-7 · Cited by 674 · see citing works
Lifespan of human lymphocyte subsets defined by CD45 isoforms
Michie, C. A., McLean, A. R., Alcock, C. J., & Beverley, P. C. L. (1992) · Nature · doi:10.1038/360264a0 · Cited by 635 · see citing works
Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry
Rufer, N., Dragowska, W. H., Thornbury, G., Roosnek, E. E., & Lansdorp, P. M. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-743 · Cited by 547 · see citing works
Shields, P. L., Morland, C. M., Salmon, M., Qin, S., Hübscher, S. G., & Adams, D. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.11.6236 · Cited by 424 · see citing works
Self-citationOehen, S., & Brduscha‐Riem, K. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.10.5338 · Cited by 366 · see citing works
Interconversion of CD45R subsets of CD4 T cells in vivo
Bell, E. B., & Sparshott, S. M. (1990) · Nature · doi:10.1038/348163a0 · Cited by 357 · see citing works
Steven, N. M., Annels, N. E., Kumar, A. A., Leese, A. M., Kurilla, M. G., & Rickinson, A. B. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.9.1605 · Cited by 350 · see citing works
Self-citationAkbar, A. N., Borthwick, N., Wickremasinghe, R. G., Panayiotidis, P. G., Pilling, D., Bofill, M., Krajewski, S., Reed, J. C., & Salmon, M. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260204 · Cited by 349 · see citing works
Self-citationCampbell, J. J., Bowman, E. P., Murphy, K. E., Youngman, K. R., Siani, M. A., Thompson, D. A., Wu, L., Zlotnik, A., & Butcher, E. C. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.1053 · Cited by 316 · see citing works
Self-citationKalams, S. A., Goulder, P., Shea, A. K., Jones, N. G., Piechocka‐Trocha, A., Ogg, G. S., & Walker, B. D. (1999) · Journal of Virology · doi:10.1128/jvi.73.8.6721-6728.1999 · Cited by 308 · see citing works
Homing of naive, memory and effector lymphocytes
Mackay, C. R. (1993) · Current Opinion in Immunology · doi:10.1016/0952-7915(93)90063-x · Cited by 285 · see citing works
Accessing Complexity: The Dynamics of Virus-Specific T Cell Responses
Doherty, P. C., & Christensen, J. P. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.561 · Cited by 279 · see citing works
Gray, C. M., Lawrence, J., Schapiro, J., Altman, J. D., Winters, M. A., Crompton, M., Loi, M., Kundu‐Raychaudhuri, S., Davis, M. M., & Merigan, T. C. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1780 · Cited by 270 · see citing works
The synergy between naive and memory T cells during activation
Akbar, A. N., Salmon, M., & Janossy, G. (1991) · Immunology Today · doi:10.1016/0167-5699(91)90050-4 · Cited by 245 · see citing works
Self-citationOn the role of antigen in maintaining cytotoxic T-cell memory.
Kündig, T. M., Bachmann, M. F., Oehen, S., Hoffmann, U., Simard, J. J. L., Kalberer, C. P., Pircher, H., Ohashi, P. S., Hengartner, H., & Zinkernagel, R. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9716 · Cited by 229 · see citing works
Cellular environments and apoptosis: tissue microenvironments control activated T-cell death
Akbar, A. N., & Salmon, M. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)01003-7 · Cited by 214 · see citing works
Self-citationSalmon, M., Pilling, D., Borthwick, N., Viner, N. J., Janossy, G., BACON, P. A., & Akbar, A. N. (1994) · European Journal of Immunology · doi:10.1002/eji.1830240417 · Cited by 196 · see citing works
Self-citationWills, M. R., Carmichael, A., Weekes, M. P., Mynard, K., Okecha, G., Hicks, R., & Sissons, J. G. P. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.12.7080 · Cited by 167 · see citing works
On T Cell Memory: Arguments for Antigen Dependence
Kündig, T. M., Bachmann, M. F., Ohashi, P. S., Pircher, H., Hengartner, H., & Zinkernagel, R. M. (1996) · Immunological Reviews · doi:10.1111/j.1600-065x.1996.tb00696.x · Cited by 111 · see citing works
Okumura, M., Fujii, Y., Inada, K., et al. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.2.429 · Cited by 109 · see citing works
Age‐related accumulation of LFA‐1high cells in a CD8+CD45RAhigh T cell population
Okumura, M., Fujii, Y., Takeuchi, Y., et al. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230512 · Cited by 100 · see citing works
Functionally Heterogeneous CD8+T-Cell Memory Is Induced by Sendai Virus Infection of Mice
Usherwood, E. J., Hogan, R. J., Crowther, G., Surman, S. L., Hogg, T. L., Altman, J. D., & Woodland, D. L. (1999) · Journal of Virology · doi:10.1128/jvi.73.9.7278-7286.1999 · Cited by 77 · see citing works
Visualization of Polyoma Virus-Specific CD8+ T Cells In Vivo During Infection and Tumor Rejection
Lukacher, A. E., Moser, J. M., Hadley, A., & Altman, J. D. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.6.3369 · Cited by 53 · see citing works
CD4+CD45RA+T cells from adults respond to recall antigens after CD28 ligation
Pilling, D., Akbar, A. N., BACON, P. A., et al. (1996) · International Immunology · doi:10.1093/intimm/8.11.1737 · Cited by 46 · see citing works
Self-citationCD45RA(bright)/CD11a(bright) CD8+ T cells: effector T cells.
Höflich, C., Döcke, W. ‐., Busch, A., Kern, F., & Volk, H. (1998) · International Immunology · doi:10.1093/intimm/10.12.1837 · Cited by 33 · see citing works
The kinetics of interaction between lymphocytes and magnetic polymer particles
Pilling, D., Kitas, G. D., Salmon, M., et al. (1989) · Journal of Immunological Methods · doi:10.1016/0022-1759(89)90269-x · Cited by 25 · see citing works
Self-citationRodriguez-Palmero, M. (1999) · doi:10.1002/(sici)1521-4141(199912)29:12
Flagged first, then by citations
Cited by
Sorted by citations
Cellular responses to viral infection in humans: lessons from Epstein–Barr virus
Hislop, A. D., Taylor, G. S., Sauce, D., & Rickinson, A. B. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141553 · Cited by 766 · see citing works
Self-citationPhenotype and function of human T lymphocyte subsets: Consensus and issues
Appay, V., van Lier, R. A. W., Sallusto, F., & Roederer, M. (2008) · Cytometry Part A · doi:10.1002/cyto.a.20643 · Cited by 729 · see citing works
Development and Homeostasis of T Cell Memory in Rhesus Macaque
Pitcher, C. J., Hagen, S. I., Walker, J. M., Lum, R., Mitchell, B. L., Maino, V. C., Axthelm, M. K., & Picker, L. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.1.29 · Cited by 467 · see citing works
p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells
Henson, S. M., Lanna, A., Riddell, N. E., Franzese, O., Macaulay, R., Griffiths, S. J., Puleston, D. J., Watson, A. S., Simon, A. K., Tooze, S. A., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75051 · Cited by 389 · see citing works
Self-citationPlunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., & Akbar, A. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7710 · Cited by 222 · see citing works
Self-citationAcute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype
Campbell, J. P., Riddell, N. E., Burns, V. E., Turner, M., van Zanten, J. J. C. S. V., Drayson, M. T., & Bosch, J. A. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.02.011 · Cited by 220 · see citing works
Dunne, P. J., Faint, J. M., Gudgeon, N. H., Fletcher, J. M., Plunkett, F. J., Soares, M. V. D., Hislop, A. D., Annels, N. E., Rickinson, A. B., Salmon, M., et al. (2002) · Blood · doi:10.1182/blood-2002-01-0160 · Cited by 144 · see citing works
Self-citationCurbishley, S. M., Eksteen, B., Gladue, R. P., Lalor, P., & Adams, D. H. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62060-3 · Cited by 141 · see citing works
Self-citationLibri, V., Azevedo, R. I., Jackson, S. E., Di Mitri, D., Lachmann, R., Fuhrmann, S., Vukmanovic-Stejic, M., Yong, K., Battistini, L., Kern, F., et al. (2011) · Immunology · doi:10.1111/j.1365-2567.2010.03386.x · Cited by 111 · see citing works
Self-citationDerhovanessian, E., Maier, A. B., Hähnel, K., Zelba, H., de Craen, A. J. M., Roelofs, H., Slagboom, E. P., Westendorp, R. G. J., & Pawelec, G. (2013) · AGE · doi:10.1007/s11357-012-9425-7 · Cited by 102 · see citing works
Waller, E. C. P., McKinney, N., Hicks, R., Carmichael, A. J., Sissons, J. G. P., & Wills, M. R. (2007) · Blood · doi:10.1182/blood-2007-07-104604 · Cited by 90 · see citing works
Dunne, P. J. (2005) · Blood · doi:10.1182/blood-2004-11-4469 · Cited by 53 · see citing works
Panoskaltsis, N., McCarthy, N. E., Stagg, A. J., Mummery, C. J., Husni, M., Arebi, N., Greenstein, D., Price, C. L., Al-Hassi, H. O., Koutinas, M., et al. (2021) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-020-02725-2 · Cited by 16 · see citing works
- Authors
- Faint, J. M., Annels, N. E., Curnow, S. J., Shields, P., Pilling, D., Hislop, A. D., Wu, L., Akbar, A. N., Buckley, C. D., Moss, P. A. H., Adams, D. H., Rickinson, A. B., & Salmon, M.
- Affiliations
- University of Birmingham/Medical Research Council Centre for Immune Regulation, University of Birmingham , Birmingham ,
- University of Birmingham (GB)
- Takeda Oncology (United States) (US)
- The Royal Free Hospital (GB)
- Corresponding author
- Shields, Philip
- Pilling, Darrell
- Salmon, Mike
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-07-01
- Volume
- 167
- Issue
- 1
- Pages
- 212-220
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2113168773
- Cited by
- 171
- References
- 41
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 1 · 2015: 7 · 2014: 8 · 2013: 1 · 2012: 6
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- 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 › Virology › HIV Research and Treatment
- Keywords
- memory T cells, CD45RO+ memory T cells, naive T cells, LFA-1, CCR7, telomere length, IFN-gamma production, IL-2 production, T cell migration, infectious mononucleosis, tetramer binding, lymph node distribution
- MeSH terms
- Cell Division, Cell Movement, Chemotaxis, Leukocyte, Humans, Immunologic Memory, Interphase, Organ Specificity, Peptide Fragments, HLA-A2 Antigen, HLA-B8 Antigen, Immunophenotyping, Lymphocyte Function-Associated Antigen-1, T-Lymphocyte Subsets, Apoptosis, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Receptors, Chemokine, Receptors, CCR5, Receptors, CCR7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
