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Longitudinal Studies of Clonally Expanded CD8 T Cells Reveal a Repertoire Shrinkage Predicting Mortality and an Increased Number of Dysfunctional Cytomegalovirus-Specific T Cells in the Very Elderly
Abstract
The age-associated decrease in functionality of the human immune system is thought to have a negative impact on the capacity to provide protection against infection, in turn leading to increased incidence of mortality. In a previous longitudinal study of octogenarians, we identified an immune risk phenotype (IRP) in the very elderly defined by an inverted CD4/CD8 ratio, which was associated with increased mortality and persistent CMV infection. In this study, we analyzed the CD8 clonal composition of nonagenarians and middle-aged individuals. An increased number of CD8 T cell clones was observed in the nonagenarians, and was associated with CMV-seropositivity. Surprisingly, CMV-seropositive nonagenarians with the IRP had a significantly lower number of clones compared with non-IRP individuals. The decrease in clone numbers in IRP individuals was associated with shorter survival time. MHC/peptide multimer staining indicated that the frequency of CMV-specific T cells was higher in nonagenarians than in the middle-aged, but the ratio of functionally intact cells was significantly lower. The lowest ratio of functional CMV-specific T cells was found in an IRP individual. A thorough longitudinal analysis of the CMV-specific T cells in nonagenarians showed a stable pattern with respect to frequency, phenotype, and clonal composition. We hypothesize that the number of different CD8 T cell clonal expansions increases as the individual ages, possibly, as a compensatory mechanism to control latent infections, e.g., CMV, but eventually a point is reached where clonal exhaustion leads to shrinkage of the CD8 clonal repertoire, associated with decreased survival.
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Citations
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 · cited 2×
“The expression of the costimulatory molecules, CD28 and CD27, tends to decrease with T cell differentiation (17, 18).”
BackgroundMethodPhenotypic 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 · cited 1×
“insight regarding the biology of Ag-specific CD8 T cells (16).”
BackgroundCentral Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance
Sallusto, F., Geginat, J., & Lanzavecchia, A. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.22.012703.104702 · Cited by 3,067
Sylwester, A. W., Mitchell, B. L., Edgar, J. B., Taormina, C., Pelte, C., Ruchti, F., Sleath, P. R., Grabstein, K. H., Hosken, N. A., Kern, F., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050882 · Cited by 1,339 · cited 1×
“very well be engaged in the natural reactivity against CMV (37).”
BackgroundAGEING, IMMUNE RESPONSE, AND MORTALITY
Roberts-Thomson, I., Youngchaiyud, U., Whittingham, S., & Mackay, I. (1974) · The Lancet · doi:10.1016/s0140-6736(74)91755-3 · Cited by 477
Wikby, A., Ferguson, F., Forsey, R., Thompson, J., Strindhall, J., Löfgren, S., Nilsson, B.-O., Ernerudh, J., Pawelec, G., & Johansson, B. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.5.556 · Cited by 407
Self-citationCell-Mediated Immunity as a Predictor of Morbidity and Mortality in Subjects Over 60
Wayne, S. J., Rhyne, R. L., Garry, P. J., & Goodwin, J. S. (1990) · Journal of Gerontology · doi:10.1093/geronj/45.2.m45 · Cited by 303 · cited 1×
“This leads to increased morbidity and mortality (3, 4).”
Background
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HIV Infection, Inflammation, Immunosenescence, and Aging
Deeks, S. G. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-042909-093756 · Cited by 1,349
Age and immunity: What is “immunosenescence”?
Pawelec, G. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2017.10.024 · Cited by 606
Self-citationSerrano-Villar, S., Sainz, T., Lee, S. A., Hunt, P. W., Sinclair, E., Shacklett, B. L., Ferre, A. L., Hayes, T. L., Somsouk, M., Hsue, P. Y., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004078 · Cited by 611
Immunosenescence and inflammaging in the aging process: age-related diseases or longevity?
Santoro, A., Bientinesi, E., & Monti, D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101422 · Cited by 603
Immunosenescence and human vaccine immune responses
Crooke, S. N., Ovsyannikova, I. G., Poland, G. A., & Kennedy, R. B. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0164-9 · Cited by 530
T cell subset-specific susceptibility to aging
Czesnikiewicz-Guzik, M., Lee, W.-W., Cui, D., Hiruma, Y., Lamar, D. L., Yang, Z.-Z., Ouslander, J. G., Weyand, C. M., & Goronzy, J. J. (2008) · Clinical Immunology · doi:10.1016/j.clim.2007.12.002 · Cited by 478
Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
Nikolich-Žugich, J. (2008) · Nature reviews. Immunology · doi:10.1038/nri2318 · Cited by 463
Human T Cell Aging and the Impact of Persistent Viral Infections
Fülöp, T., Larbi, A., & Pawelec, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00271 · Cited by 347
Self-citationImmunosenescence and vaccine failure in the elderly
Grubeck-Loebenstein, B., Della Bella, S., Iorio, A. M., Michel, J.-P., Pawelec, G., & Solana, R. (2009) · Aging Clinical and Experimental Research · doi:10.1007/bf03324904 · Cited by 269
Self-citationAging of the T Cell Compartment in Mice and Humans: From No Naive Expectations to Foggy Memories
Nikolich-Žugich, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401174 · Cited by 259
Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence
KOCH, S., LARBI, A., ÖZCELIK, D., SOLANA, R., GOUTTEFANGEAS, C., ATTIG, S., WIKBY, A., STRINDHALL, J., FRANCESCHI, C., & PAWELEC, G. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1396.043 · Cited by 242
Self-citationWang, G. C., Dash, P., McCullers, J. A., Doherty, P. C., & Thomas, P. G. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003647 · Cited by 238
McElhaney, J. E., Zhou, X., Talbot, H. K., Soethout, E., Bleackley, R. C., Granville, D. J., & Pawelec, G. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.01.015 · Cited by 229
Self-citationBiomarkers of human immunosenescence: impact of cytomegalovirus infection
Derhovanessian, E., Larbi, A., & Pawelec, G. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.012 · Cited by 220
Self-citationStrindhall, J., Nilsson, B.-O., Löfgren, S., Ernerudh, J., Pawelec, G., Johansson, B., & Wikby, A. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.05.001 · Cited by 209
Self-citationRole of CMV in immune senescence.
Pawelec, G., & Derhovanessian, E. (2011) · Virus Research · doi:10.1016/j.virusres.2010.09.010 · Cited by 201
Self-citationVescovini, R., Biasini, C., Fagnoni, F. F., Telera, A. R., Zanlari, L., Pedrazzoni, M., Bucci, L., Monti, D., Medici, M. C., Chezzi, C., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4283 · Cited by 173
Derhovanessian, E., Solana, R., Larbi, A., & Pawelec, G. (2008) · Immunity & Ageing · doi:10.1186/1742-4933-5-11 · Cited by 169
Self-citationImmunosenenescence: role of cytomegalovirus
Pawelec, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.010 · Cited by 163
Self-citationLurain, N. S., Hanson, B. A., Martinson, J., Leurgans, S. E., Landay, A. L., Bennett, D. A., & Schneider, J. A. (2013) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit210 · Cited by 159
Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates
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Weltevrede, M., Eilers, R., de Melker, H. E., & van Baarle, D. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.02.005 · Cited by 128
Immunology of the ageing kidney
Sato, Y., & Yanagita, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0185-9 · Cited by 126
Derhovanessian, E., Theeten, H., Hähnel, K., Van Damme, P., Cools, N., & Pawelec, G. (2013) · Vaccine · doi:10.1016/j.vaccine.2012.11.041 · Cited by 121
Self-citationCytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine
Frasca, D., Diaz, A., Romero, M., Landin, A. M., & Blomberg, B. B. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.01.071 · Cited by 116
Boyajian, J. L., Ghebretatios, M., Schaly, S., Islam, P., & Prakash, S. (2021) · Nutrients · doi:10.3390/nu13124550 · Cited by 115
Derhovanessian, 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
Self-citationNew tools for classification and monitoring of autoimmune diseases
Maecker, H. T., Lindstrom, T. M., Robinson, W. H., Utz, P. J., Hale, M., Boyd, S. D., Shen-Orr, S. S., & Fathman, C. G. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.66 · Cited by 95
Johnson, P. L. F., Yates, A. J., Goronzy, J. J., & Antia, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1209283110 · Cited by 94
Aging, immune senescence, and immunotherapy: a comprehensive review
Elias, R., Hartshorn, K., Rahma, O., Lin, N., & Snyder-Cappione, J. E. (2018) · Seminars in Oncology · doi:10.1053/j.seminoncol.2018.08.006 · Cited by 96
Can blocking inflammation enhance immunity during aging?
Chambers, E. S., & Akbar, A. N. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.016 · Cited by 92
Turner, J. E., Aldred, S., Witard, O. C., Drayson, M. T., Moss, P. M., & Bosch, J. A. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.07.239 · Cited by 90
Parish, S. T., Wu, J. E., & Effros, R. B. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9449-7 · Cited by 85
Age-Associated Increase of Low-Avidity Cytomegalovirus-Specific CD8+ T Cells That Re-Express CD45RA
Griffiths, S. J., Riddell, N. E., Masters, J., Libri, V., Henson, S. M., Wertheimer, A., Wallace, D., Sims, S., Rivino, L., Larbi, A., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203267 · Cited by 82
Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
Merani, S., Pawelec, G., Kuchel, G. A., & McElhaney, J. E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00784 · Cited by 74
Self-citationGil, A., Yassai, M. B., Naumov, Y. N., & Selin, L. K. (2015) · Journal of Virology · doi:10.1128/jvi.03020-14 · Cited by 78
The emerging role of ECM crosslinking in T cell mobility as a hallmark of immunosenescence in humans
Moreau, J.-F., Pradeu, T., Grignolio, A., Nardini, C., Castiglione, F., Tieri, P., Capri, M., Salvioli, S., Taupin, J.-L., Garagnani, P., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.11.005 · Cited by 67
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Aiello, A. E., Dowd, J. B., Jayabalasingham, B., Feinstein, L., Uddin, M., Simanek, A. M., Cheng, C. K., Galea, S., Wildman, D. E., Koenen, K., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.01.024 · Cited by 66
Self-citationThe silent war of CMV in aging and HIV infection
Effros, R. B. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.09.003 · Cited by 63
Variability in the immune system: of vaccine responses and immune states
Shen-Orr, S. S., & Furman, D. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.07.009 · Cited by 61
Ng, T. P., Camous, X., Nyunt, M. S. Z., Vasudev, A., Tan, C. T. Y., Feng, L., Fulop, T., Yap, K. B., & Larbi, A. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.5 · Cited by 58
Muller, G. C., Gottlieb, M. G. V., Luz Correa, B., Filho, I. G., Moresco, R. N., & Bauer, M. E. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.05.006 · Cited by 55
Vescovini, R., Fagnoni, F. F., Telera, A. R., Bucci, L., Pedrazzoni, M., Magalini, F., Stella, A., Pasin, F., Medici, M. C., Calderaro, A., et al. (2014) · AGE · doi:10.1007/s11357-013-9594-z · Cited by 48
Arnold, C. R., Pritz, T., Brunner, S., Knabb, C., Salvenmoser, W., Holzwarth, B., Thedieck, K., & Grubeck-Loebenstein, B. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.018 · Cited by 42
Age-Related Adaptive Immune Changes in Parkinson’s Disease
Kouli, A., & Williams-Gray, C. H. (2022) · Journal of Parkinson's Disease · doi:10.3233/jpd-223228 · Cited by 20
Metadata
- Authors
- Hadrup, S. R., Strindhall, J., Køllgaard, T., Seremet, T., Johansson, B., Pawelec, G., thor Straten, P., & Wikby, A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02
- Volume
- 176
- Issue
- 4
- Pages
- 2645-2653
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1533059496
- Cited by
- 471
- References
- 7
- FWCI
- 8.24
- Type
- journal article
- Language
- en
- Open access
- closed
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