Replicative senescence of CD8 T cells: Effect on human ageing

Effros, Rita B.

doi:10.1016/j.exger.2003.09.024

Cited by 127Telomeres, Telomerase, and SenescenceT-cell and B-cell ImmunologyGenetics, Aging, and Longevity in Model Organisms

Replicative senescence of CD8 T cells: Effect on human ageing

Effros, Rita B.·2004·Experimental Gerontology

DOI 10.1016/j.exger.2003.09.024

Open this paper in CoChat — free account

Abstract

Elderly persons have been exposed to a myriad of pathogens over their lifespan. This life-long immunological history leads, in some cases, to the generation of expanded populations of memory CD8 T cells that have reached the end stage of replicative senescence. In cell culture, CD8 T cells that are subjected to repeated rounds of antigen-driven proliferation eventually show irreversible cell cycle arrest, permanent and complete loss of CD28 gene expression, apoptosis resistance, reduced gene transcription of the major stress protein in response to heat shock, and shortened telomeres compared to their CD28-expressing progenitors. Clinical studies have documented that high proportions of CD8 T cells that lack CD28 are correlated with reduced antibody response to influenza vaccination and are also an immune marker of increased risk of mortality in persons greater than 80 years of age. In addition, CD8 T cells lacking CD28 expression have been documented to have suppressive influences on immune function. Thus, senescent CD8 T cells may affect immune function both directly and indirectly by modulating other immune cell types. The potential role of senescent T cells in bone homeostasis is suggested as a potentially fruitful area for future investigation. The patterns of cytokine changes observed during the progression to senescence in cell culture are consistent with this possibility, and T cells producing these same cytokines have, in fact, been identified within the bone marrow in murine models of osteoporosis. Interestingly, CD8 T cells with markers of replicative senescence are correlated with increased osteoporotic fractures in the elderly. Thus, senescent CD8 T cells are associated with a variety of deleterious health-related outcomes, suggesting that these cells may exert pleiotropic negative effects on both immune and non-immune organ systems during ageing.

Integrity signals

Registry

Crossref · 10.1016/j.exger.2003.09.024

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Telomere length of CD28+ T cells is longer than that of more differentiated lines such as CD28− or CD8+ T cells.
“The same stands for CD28+ T cells as compared to more differentiated lines such as CD28− or CD8+ T cells [225,226].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [225]

Marrow Stromal Cells as Stem Cells for Nonhematopoietic Tissues
Prockop, D. J. (1997) · Science · doi:10.1126/science.276.5309.71 · Cited by 4,629 · see citing works
CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717 · see citing works
CD4+CD25+ suppressor T cells: more questions than answers
Shevach, E. M. (2002) · Nature reviews. Immunology · doi:10.1038/nri821 · Cited by 2,097 · see citing works
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging
Krtolica, A., Parrinello, S., Lockett, S., Desprez, P.-Y., & Campisi, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211053698 · Cited by 1,730 · see citing works
T-Cell mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ.
Takayanagi, H., Ogasawara, K., Hida, S., Chiba, T., Murata, S., Sato, K., Takaoka, A., Yokochi, T., Oda, H., Tanaka, K., et al. (2000) · Nature · doi:10.1038/35046102 · Cited by 1,358 · see citing works
Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells
Brenchley, J. M., Karandikar, N. J., Betts, M. R., Ambrozak, D. R., Hill, B. J., Crotty, L. E., Casazza, J. P., Kuruppu, J., Migueles, S. A., Connors, M., et al. (2003) · Blood · doi:10.1182/blood-2002-07-2103 · Cited by 1,073 · see citing works
Age, Thymopoiesis, and CD4+ T-Lymphocyte Regeneration after Intensive Chemotherapy
Mackall, C. L., Fleisher, T. A., Brown, M. R., Andrich, M. P., Chen, C. C., Feuerstein, I. M., Horowitz, M. E., Magrath, I. T., Shad, A. T., Steinberg, S. M., et al. (1995) · New England Journal of Medicine · doi:10.1056/nejm199501193320303 · Cited by 1,026 · see citing works
A Gender Gap in Autoimmunity: Task Force on Gender, Multiple Sclerosis and Autoimmunity
Whitacre, C. C., Reingold, S. C., O'Looney, P. A., Blankenhorn, E., Brinley, F., Collier, E., Duquette, P., Fox, H., Giesser, B., Gilmore, W., et al. (1999) · Science · doi:10.1126/science.283.5406.1277 · Cited by 851 · see citing works
Bone versus immune system
Arron, J. R., & Choi, Y. (2000) · Nature · doi:10.1038/35046196 · Cited by 828 · see citing works
Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy".
Posnett, D. N., Sinha, R., Kabak, S., & Russo, C. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.609 · Cited by 761 · see citing works
Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals
Khan, N., Shariff, N., Cobbold, M., Bruton, R., Ainsworth, J. A., Sinclair, A. J., Nayak, L., & Moss, P. A. H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.4.1984 · Cited by 754 · see citing works
Cutting Edge: Regulatory T Cells from Lung Cancer Patients Directly Inhibit Autologous T Cell Proliferation
Woo, E. Y., Yeh, H., Chu, C., Schlienger, K., Carroll, R. G., Riley, J. L., Kaiser, L. R., & June, C. H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.9.4272 · Cited by 689 · see citing works
Up-regulation of TNF-producing T cells in the bone marrow: A key mechanism by which estrogen deficiency induces bone loss <i>in vivo</i>
Roggia, C., Gao, Y., Cenci, S., Weitzmann, M. N., Toraldo, G., Isaia, G., & Pacifici, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251534698 · Cited by 513 · see citing works
Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines
Saurwein-Teissl, M., Lung, T. L., Marx, F., Gschösser, C., Asch, E., Blasko, I., Parson, W., Böck, G., Schönitzer, D., Trannoy, E., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5893 · Cited by 499 · see citing works
Suppressor T Cells
Gershon, R. K., Cohen, P., Hencin, R. S., & Liebhaber, S. A. (1972) · The Journal of Immunology · doi:10.4049/jimmunol.108.3.586 · Cited by 463 · see citing works
Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis
Effros, R. B., Allsopp, R., Chiu, C.-P., Hausner, M. A., Hirji, K., Wang, L., Harley, C. B., Villeponteau, B., West, M. D., & Giorgi, J. V. (1996) · AIDS · doi:10.1097/00002030-199607000-00001 · Cited by 457 · see citing works
Self-citation
Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time
Karrer, U. W., Sierro, S. R., Wagner, M., Oxenius, A., Hengel, H., Koszinowski, U. H., Phillips, R. E., & Klenerman, P. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.4.2022 · Cited by 444 · see citing works
Population Biology of Lymphocytes: The Flight for Survival
Freitas, A. A., & Rocha, B. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.83 · Cited by 426 · see citing works
Estrogen regulates the IFN-gamma promoter
Fox, H. S., Bond, B. L., & Parslow, T. G. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.12.4362 · Cited by 424 · see citing works
Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals
Goronzy, J. J., Fulbright, J. W., Crowson, C. S., Poland, G. A., O'Fallon, W. M., & Weyand, C. M. (2001) · Journal of Virology · doi:10.1128/jvi.75.24.12182-12187.2001 · Cited by 402 · see citing works
CD28- T lymphocytes. Antigenic and functional properties
Azuma, M., Phillips, J. H., & Lanier, L. L. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.150.4.1147 · Cited by 392 · see citing works
Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study
Wikby, A., Maxson, P., Olsson, J., Johansson, B. E. A., & Ferguson, F. G. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00151-6 · Cited by 377 · see citing works
CD28, CTLA‐4 and their ligands: who does what and to whom?
Sansom, D. M. (2000) · Immunology · doi:10.1046/j.1365-2567.2000.00121.x · Cited by 362 · see citing works
Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo
Rocha, B., Dautigny, N., & Pereira, P. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190518 · Cited by 343 · see citing works
Characterization of human bone marrow stromal cells with respect to osteoblastic differentiation
Majors, A. K., Boehm, C., Nitto, H., Midura, R. J., & Muschler, G. F. (1997) · Journal of Orthopaedic Research® · doi:10.1002/jor.1100150410 · Cited by 332 · see citing works
Soluble HLA-G protein secreted by allo-specific CD4 + T cells suppresses the allo-proliferative response: A CD4 + T cell regulatory mechanism
Lila, N., Rouas‐Freiss, N., Dausset, J. B., Carpentier, A., & Carosella, E. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201407398 · Cited by 313 · see citing works
Expanded CD4+ and CD8+ T cell clones in elderly humans
Schwab, R., Szabó, P. E., Manavalan, J. S., Weksler, M. E., Posnett, D. N., Pannetier, C., Kourilsky, P., & Even, J. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.9.4493 · Cited by 291 · see citing works
Estrogens, the immune response and autoimmunity.
Cutolo, M., Sulli, A., SERIOLO, B., Accardo, S., & Masi, A. T. (1995) · PubMed · Cited by 288 · see citing works
Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells
Bynoe, M. S., Grimaldi, C. M., & Diamond, B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040577497 · Cited by 279 · see citing works
Suppressor T cells – they’re back and critical for regulation of autoimmunity!
Chatenoud, L., Salomon, B. L., & Bluestone, J. A. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1820112.x · Cited by 275 · see citing works
Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines
Weitzmann, M. N., Cenci, S., Rifas, L., Brown, C., & Pacifici, R. (2000) · Blood · doi:10.1182/blood.v96.5.1873 · Cited by 265 · see citing works
From cells to organisms: can we learn about aging from cells in culture?
Campisi, J. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00230-8 · Cited by 263 · see citing works
Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation☆
Spaulding, C., Guo, W., & Effros, R. B. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00033-9 · Cited by 258 · see citing works
Self-citation
Divergent Telomerase and CD28 Expression Patterns in Human CD4 and CD8 T Cells Following Repeated Encounters with the Same Antigenic Stimulus
Valenzuela, H. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5271 · Cited by 254 · see citing works
Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells
Misiti, S., Nanni, S., Fontemaggi, G., Cong, Y.-S., Wen, J., Hirte, H. W., Piaggio, G., Sacchi, A., Pontecorvi, A., Bacchetti, S., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.3764-3771.2000 · Cited by 254 · see citing works
Role of Cytomegalovirus in the T Cell Changes Seen in Elderly Individuals
Looney, R. J., Falsey, A. R., Campbell, D., Torres, A., Kolassa, J. E., Brower, C., McCann, R. M., Menegus, M. A., McCormick, K., Frampton, M. W., et al. (1999) · Clinical Immunology · doi:10.1006/clim.1998.4638 · Cited by 243 · see citing works
CD4+ regulatory T cells
Read, S., & Powrie, F. M. (2001) · Current Opinion in Immunology · doi:10.1016/s0952-7915(01)00273-4 · Cited by 228 · see citing works
Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28− cytotoxic effector clones
Posnett, D. N., Edinger, J. W., Manavalan, J. S., Irwin, C., & Marodon, G. (1999) · International Immunology · doi:10.1093/intimm/11.2.229 · Cited by 202 · see citing works
CD28 Expression in T Cell Aging and Human Longevity
Boucher, N., Dufeu-Duchesne, T., Vicaut, E., Farge, D., Effros, R. B., & Schächter, F. (1998) · Experimental Gerontology · doi:10.1016/s0531-5565(97)00132-0 · Cited by 194 · see citing works
Self-citation
Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.
Shimizu, Y., van Seventer, G. A., Ennis, E. A., Newman, W., Horgan, K. J., & Shaw, S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.2.577 · Cited by 190 · see citing works
CD8+CD28− T suppressor cells and the induction of antigen‐specific, antigen‐presenting cell‐mediated suppression of Th reactivity
Cortesini, R., LeMaoult, J., Ciubotariu, R., & Cortesini, N. S.-F. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1820116.x · Cited by 185 · see citing works
Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta.
Somasundaram, R., Jacob, L., Swoboda, R., Caputo, L., Song, H., Basak, S. K., Monos, D. S., Peritt, D., Marincola, F. M., Cai, D., et al. (2002) · PubMed · Cited by 181 · see citing works
The Role of Cellular Senescence in Skin Aging
Campisi, J. (1998) · Journal of Investigative Dermatology Symposium Proceedings · doi:10.1038/jidsymp.1998.2 · Cited by 177 · see citing works
Oestrogen and Human T Lymphocytes: Presence of Specific Receptors in the T‐Suppressor/Cytotoxic Subset
STIMSON, W. H. (1988) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.1988.tb01459.x · Cited by 164 · see citing works
Osteoprotegerin ligand: a regulator of immune responses and bone physiology
Kong, Y., Boyle, W. J., & Penninger, J. M. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01718-7 · Cited by 160 · see citing works
Immune cell circulating subsets are affected by gonadal function
Giglio, T., Imro, M. A., Filaci, G., SCUDELETTI, M., Puppo, F., Cecco, L. D., Indiveri, F., & Costantini, S. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00508-7 · Cited by 154 · see citing works
Interactions between immune and bone cells: new insights with many remaining questions
Lorenzo, J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11089 · Cited by 152 · see citing works
Aging and T-cell-mediated immunity
Chakravarti, B., & Abraham, G. N. (1999) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(99)00009-3 · Cited by 142 · see citing works
CD4+CD25+ T Cells Facilitate the Induction of T Cell Anergy
Ermann, J., Szanya, V., Ford, G. S., Paragas, V. B., Fathman, C. G., & Lejon, K. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.8.4271 · Cited by 133 · see citing works
Subset-Specific Effects of Sex Hormones and Pituitary Gonadotropins on Human Lymphocyte Proliferation in Vitro
Athreya, B. H., Pletcher, J. R., Zulian, F., Weiner, D. B., & Williams, W. V. (1993) · Clinical Immunology and Immunopathology · doi:10.1006/clin.1993.1026 · Cited by 127 · see citing works
Peripheral expansion of pre-existing mature T cells is an important means of CD4+ T-cell regeneration HIV-infected adults
WALKER, R. E., Carter, C. S., Muul, L. M., Natarajan, V., Herpin, B. R., Leitman, S. F., Klein, H. G., Mullen, C. A., Metcalf, J. A., Baseler, M., et al. (1998) · Nature Medicine · doi:10.1038/nm0798-852 · Cited by 117 · see citing works
A Stochastic Model of Cell Replicative Senescence Based on Telomere Shortening, Oxidative Stress, and Somatic Mutations in Nuclear and Mitochondrial DNA
Sozou, P. D., & Kirkwood, T. B. L. (2001) · Journal of Theoretical Biology · doi:10.1006/jtbi.2001.2432 · Cited by 115 · see citing works
T lymphocytes play a critical role in the development of cyclosporin A- induced osteopenia
Buchinsky, F. J., Ma, Y. F., Mann, G. N., Rucinski, B., Bryer, H. P., Romero, D. F., Jee, W. S. S., & Epstein, S. (1996) · Endocrinology · doi:10.1210/endo.137.6.8641176 · Cited by 113 · see citing works
Virus-Induced CD8+ T Cell Clonal Expansion Is Associated with Telomerase Up-Regulation and Telomere Length Preservation: A Mechanism for Rescue from Replicative Senescence
Maini, M. K., Soares, M. V. D., Zilch, C. F., Akbar, A. N., & Beverley, P. C. L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4521 · Cited by 110 · see citing works
The T cell in the ageing individual1This article is based on a presentation to the First International Conference on Aging and Immunology, Bethesda, MD, 16–19 June, 1996.1
Pawelec, G., Adibzadeh, M., Solana, R., & Beckman, I. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01812-x · Cited by 109 · see citing works
The flow cytometric analysis of telomere length in antigen-specific CD8+ T cells during acute Epstein-Barr virus infection
Plunkett, F. J., Soares, M. V. D., Annels, N. E., Hislop, A. D., Ivory, K., Lowdell, M. W., Salmon, M., Rickinson, A. B., & Akbar, A. N. (2001) · Blood · doi:10.1182/blood.v97.3.700 · Cited by 109 · see citing works
Circulating cytotoxic CD8+ CD28- T cells in ankylosing spondylitis
Schirmer, M., Goldberger, C., Würzner, R., Duftner, C., Pfeiffer, K. P., Clausen, J., Neumayr, G., & Falkenbach, A. (2001) · Arthritis Research & Therapy · doi:10.1186/ar386 · Cited by 108 · see citing works
Replicative senescence in the immune system: impact of the Hayflick limit on T-cell function in the elderly
Effros, R. B. (1998) · The American Journal of Human Genetics · doi:10.1086/301845 · Cited by 105 · see citing works
Self-citation
Interferon α down-regulates telomerase reverse transcriptase and telomerase activity in human malignant and nonmalignant hematopoietic cells
Xu, D., Erickson, S., Szeps, M., Gruber, A., Sangfelt, O., Einhorn, S., Pisa, P., & Grandér, D. (2000) · Blood · doi:10.1182/blood.v96.13.4313 · Cited by 104 · see citing works
Cellular Senescence and Tissue Aging In Vivo
Hornsby, P. J. (2002) · The Journals of Gerontology Series A · doi:10.1093/gerona/57.7.b251 · Cited by 91 · see citing works
Benign Monoclonal Gammopathy
Hickman, S. (1982) · Archives of Internal Medicine · doi:10.1001/archinte.1982.00340150149025 · Cited by 89 · see citing works
A role for CD8+ T lymphocytes in osteoclast differentiation in vitro
John, V., Hock, J. M., Short, L. L., Glasebrook, A. L., & Galvin, R. J. (1996) · Endocrinology · doi:10.1210/endo.137.6.8641199 · Cited by 88 · see citing works
Age-related attenuation in the expression of the major heat shock proteins in human peripheral lymphocytes
Rao, D. V., Watson, K., & Jones, G. L. (1999) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00143-2 · Cited by 87 · see citing works
Alterations in levels of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of multiple sclerosis patients
Crucian, B. E., Dunne, P. B., Friedman, H. P., Ragsdale, R., Pross, S. H., & Widen, R. H. (1995) · Clinical and Diagnostic Laboratory Immunology · doi:10.1128/cdli.2.2.249-252.1995 · Cited by 86 · see citing works
Differential Impairment of Lytic and Cytokine Functions in Senescent Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes
Dagarag, M. D., Ng, H. L., Lubong, R., Effros, R. B., & Yang, O. O. (2003) · Journal of Virology · doi:10.1128/jvi.77.5.3077-3083.2003 · Cited by 85 · see citing works
Self-citation
The Role of Cellular Senescence in Skin Aging
Campisi, J. (1998) · Journal of Investigative Dermatology · doi:10.1038/jidsp.1998.2 · Cited by 83 · see citing works
CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity
Mollet, L. (1998) · International Immunology · doi:10.1093/intimm/10.3.311 · Cited by 81 · see citing works
Costimulatory mechanisms in the elderly
Effros, R. B. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00503-4 · Cited by 79 · see citing works
Self-citation
CD8+CD28– T cells: Certainties and uncertainties of a prevalent human T‐cell subset
Arosa, F. A. (2002) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.2002.01057.x · Cited by 73 · see citing works
Stress Response of Senescent T Lymphocytes Reduced hsp70 Is Independent of the Proliferative Block
Effros, R. B., Zhu, X., & Walford, R. L. (1994) · Journal of Gerontology · doi:10.1093/geronj/49.2.b65 · Cited by 72 · see citing works
Self-citation
Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures
Pietschmann, P., Grisar, J. C., Thien, R., Willheim, M., Kerschan‐Schindl, K., Preisinger, E., & Peterlik, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00125-5 · Cited by 69 · see citing works
An integrative model of regulation centered on recognition of TCR peptide/MHC complexes
Kumar, V., & Sercarz, E. E. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1820109.x · Cited by 63 · see citing works
An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients
Sadat-Sowti, B., Debré, P., Mollet, L., Quint, L., Hadida, F., Leblond, V., Bismuth, G., & Autran, B. (1994) · European Journal of Immunology · doi:10.1002/eji.1830241145 · Cited by 63 · see citing works
T cells: A proliferation of costimulatory molecules
Mueller, D. L. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00400-0 · Cited by 54 · see citing works
Regulation of apoptosis resistance and ontogeny of age-dependent diseases
Wang, E. (1997) · Experimental Gerontology · doi:10.1016/s0531-5565(96)00156-8 · Cited by 53 · see citing works
Differential regulation of CD8+ T cell senescence in mice and men
Akbar, A. N., Soares, M. V. D., Plunkett, F. J., & Salmon, M. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00198-6 · Cited by 46 · see citing works
In vitro senescence models for human T lymphocytes
Pawelec, G., Adibzadeh, M., Rehbein, A., Hähnel, K., Wagner, W., & Engel, A. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00504-6 · Cited by 45 · see citing works
Estrogen‐Receptor Expression and Function in Thymocytes in Relation to Gender and Age
Kohen, F., Abel, L., Sharp, A., Amir-Zaltsman, Y., Sömjen, D., Luria, S., Mor, G., Knyszynski, A., Thole, H., & Globerson, A. (1997) · Journal of Immunology Research · doi:10.1155/1998/62380 · Cited by 41 · see citing works
Human memory T cells: lessons from stem cell transplantation
Rufer, N., Helg, C., Chapuis, B., & Roosnek, E. E. (2001) · Trends in Immunology · doi:10.1016/s1471-4906(00)01849-4 · Cited by 27 · see citing works
CD28 and T cell co-stimulation.
Holdorf, A. D., Kanagawa, O., & Shaw, A. S. (2000) · PubMed · Cited by 26 · see citing works
CD4+CD25+ T Lymphocytes in Human Tonsils Suppress the Proliferation of CD4+CD25– Tonsil Cells
Simark‐Mattsson, C., Dahlgren, U. I., & Roos, K. (2002) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2002.01095.x · Cited by 18 · see citing works
Role of Regulatory T Cells in the Pathogenesis of Autoimmune Diabetes
Arreaza, G., Sharif, S., Cameron, M. J., Chen, W., & Delovitch, T. L. (2001) · KARGER eBooks · doi:10.1159/000060542 · Cited by 7 · see citing works
Untitled work
(2002) · doi:10.1002/1521-4141(200206)32:6

Flagged first, then by citations

2 of the 85 references couldn’t be matched to a known paper.

Sorted by citations

Inflamm‐ageing and lifelong antigenic load as major determinants of ageing rate and longevity
Martinis, M. D., Franceschi, C., Monti, D., & Ginaldi, L. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.02.055 · Cited by 488 · see citing works
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Akbar, A. N., & Henson, S. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2959 · Cited by 474 · see citing works
CD28 extinction in human T cells: altered functions and the program of T‐cell senescence
Vallejo, A. N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00256.x · Cited by 435 · see citing works
Osteoporosis, inflammation and ageing
Ginaldi, L., Di Benedetto, M. C., & De Martinis, M. (2005) · Immunity & Ageing · doi:10.1186/1742-4933-2-14 · Cited by 412 · see citing works
Inflammation markers predicting frailty and mortality in the elderly
Martinis, M. D., Franceschi, C., Monti, D., & Ginaldi, L. (2006) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2005.11.004 · Cited by 341 · see citing works
T Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323 · see citing works
Self-citation
Reversible Senescence in Human CD4+CD45RA+CD27− Memory T Cells
Di Mitri, D., Azevedo, R. I., Henson, S. M., Libri, V., Riddell, N. E., Macaulay, R., Kipling, D., Soares, M. V. D., Battistini, L., & Akbar, A. N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100978 · Cited by 231 · see citing works
Properties of end-stage human T cells defined by CD45RA re-expression
Henson, S. M., Riddell, N. E., & Akbar, A. N. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.04.001 · Cited by 180 · see citing works
“Social Life” of Senescent Cells: What Is SASP and Why Study It?
Borodkina, A. V., Deryabin, P. I., Giukova, А. А., & Nikolsky, N. N. (2018) · Acta Naturae · doi:10.32607/20758251-2018-10-1-4-14 · Cited by 170 · see citing works
Parallels in Immunometabolic Adipose Tissue Dysfunction with Ageing and Obesity
Trim, W. V., Turner, J. E., & Thompson, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00169 · Cited by 167 · see citing works
p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes
Mondal, A. M., Horikawa, I., Pine, S. R., Fujita, K., Morgan, K. M., Vera, E., Mazur, S. J., Appella, E., Vojtesek, B., Blasco, M. A., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70355 · Cited by 164 · see citing works
Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis
Valdes, A. M., Richards, J. B., Gardner, J. P., Swaminathan, R., Kimura, M., Xiaobin, L., Aviv, A., & Spector, T. D. (2007) · Osteoporosis International · doi:10.1007/s00198-007-0357-5 · Cited by 164 · see citing works
Age-related decline in immunity: implications for vaccine responsiveness
Kumar, R., & Burns, E. A. (2008) · Expert Review of Vaccines · doi:10.1586/14760584.7.4.467 · Cited by 156 · see citing works
Estrogen deficiency, T cells and bone loss
Pacifici, R. (2008) · Cellular Immunology · doi:10.1016/j.cellimm.2007.06.008 · Cited by 146 · see citing works
Leukocyte function in the aging immune system
Desai, A., Grolleau‐Julius, A., & Yung, R. L. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0809542 · Cited by 141 · see citing works
Role of CD8 T Cell Replicative Senescence in Human Aging and in HIV-mediated Immunosenescence.
Dock, J., & Effros, R. B. (2011) · Europe PMC (PubMed Central) · Cited by 137 · see citing works
Self-citation
Cellular senescence, ageing and disease
Burton, D. G. A. (2008) · AGE · doi:10.1007/s11357-008-9075-y · Cited by 135 · see citing works
Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir
Brown, T. T., Moser, C., Currier, J. S., Ribaudo, H. J., Rothenberg, J., Kelesidis, T., Yang, O. O., Dubé, M. P., Murphy, R. L., Stein, J. H., et al. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv194 · Cited by 120 · see citing works
Host Resistance and Immune Responses in Advanced Age
Castle, S. C., Uyemura, K., Fülöp, T., & Makinodan, T. (2007) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2007.03.005 · Cited by 118 · see citing works
The Single-Cell Phenotypic Identity of Human CD8+ and CD4+ T Cells
Brummelman, J., Pilipow, K., & Lugli, E. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.05.007 · Cited by 110 · see citing works
ROS as signalling molecules in T cells – evidence for abnormal redox signalling in the autoimmune disease, rheumatoid arthritis
Griffiths, H. R. (2005) · Redox Report · doi:10.1179/135100005x83680 · Cited by 103 · see citing works
High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects
Simpson, R. J., Florida-James, G. D., Cosgrove, C., Whyte, G. P., Macrae, S., Pircher, H., & Guy, K. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00007.2007 · Cited by 101 · see citing works
Senescent T-lymphocytes are mobilised into the peripheral blood compartment in young and older humans after exhaustive exercise
Simpson, R. J., Cosgrove, C., Ingram, L. A., Florida-James, G. D., Whyte, G. P., Pircher, H., & Guy, K. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.11.002 · Cited by 99 · see citing works
Dendritic cells and aging: consequences for autoimmunity
Agrawal, A., Sridharan, A., Prakash, S., & Agrawal, H. (2011) · Expert Review of Clinical Immunology · doi:10.1586/eci.11.77 · Cited by 89 · see citing works
Influenza-Induced Production of Interferon-Alpha is Defective in Geriatric Individuals
Canaday, D. H., Amponsah, N. A., Jones, L., Tisch, D. J., Hornick, T. R., & Ramachandra, L. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9374-9 · Cited by 89 · see citing works
T Cells: Unexpected Players in the Bone Loss Induced by Estrogen Deficiency and in Basal Bone Homeostasis
Weitzmann, M. N., & Pacifici, R. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1402.068 · Cited by 88 · see citing works
Modulation of T Lymphocyte Replicative Senescence via TNF-α Inhibition: Role of Caspase-3
Parish, S. T., Wu, J. E., & Effros, R. B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803449 · Cited by 86 · see citing works
Self-citation
Sustained CD28 Expression Delays Multiple Features of Replicative Senescence in Human CD8 T Lymphocytes
Parish, S. T., Wu, J. E., & Effros, R. B. (2010) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9449-7 · Cited by 85 · see citing works
Self-citation
Impaired secretion of interferons by dendritic cells from aged subjects to influenza
Prakash, S., Agrawal, S., Cao, J., Gupta, S., & Agrawal, A. (2012) · AGE · doi:10.1007/s11357-012-9477-8 · Cited by 80 · see citing works
The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome
Plunkett, F. J., Franzese, O., Belaramani, L. L., Fletcher, J. M., Gilmour, K. C., Sharifi, R., Khan, N., Hislop, A. D., Cara, A., Salmon, M., et al. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.03.006 · Cited by 74 · see citing works
Immunosupportive therapies in aging
Fülöp, T., Larbi, A., Hirokawa, K., Mocchegiani, E., Lesourd, B., Castle, S., Wikby, A., Franceschi, C., & Pawelec, G. (2007) · Clinical Interventions in Aging · doi:10.2147/ciia.2007.2.1.33 · Cited by 71 · see citing works
Dysregulation of CD8+ lymphocyte apoptosis, chronic disease, and immune regulation
Karen, L. W. (2009) · Frontiers in bioscience · doi:10.2741/3487 · Cited by 64 · see citing works
Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity
Bernabeu‐Wittel, M., Gómez-Díaz, R., González-Molina, Á., Serrano, S. V., Díez‐Manglano, J., Salgado, F., Soto-Martín, M., Ollero‐Baturone, M., & RESEARCHERS, O. B. O. T. P. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9082669 · Cited by 64 · see citing works
Immune memory and aging: an infinite or finite resource?
Nikolich-Žugich, J., & Rudd, B. D. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.06.011 · Cited by 58 · see citing works
Cellular aging and senescence characteristics of human T-lymphocytes
Onyema, O. O., Njemini, R., Bautmans, I., Renmans, W., Waele, M. D., & Mets, T. F. (2011) · Biogerontology · doi:10.1007/s10522-011-9366-z · Cited by 57 · see citing works
Immunosenescence and Anti-Immunosenescence Therapies: The Case of Probiotics
Candore, G., Balistreri, C. R., Colonna‐Romano, G., Grimaldi, M. P., Lio, D., Listı̀, F., Scola, L., Vasto, S., & Caruso, C. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0662 · Cited by 55 · see citing works
The effect of aging, nutrition, and exercise during HIV infection
Miller, T. L., Somarriba, Neri, D. A., & Schaefer (2010) · HIV/AIDS - Research and Palliative Care · doi:10.2147/hiv.s9069 · Cited by 48 · see citing works
Immune resilience in HIV-infected individuals seronegative for cytomegalovirus
Barrett, L., Stapleton, S. N., Fudge, N. J., & Grant, M. D. (2014) · AIDS · doi:10.1097/qad.0000000000000405 · Cited by 43 · see citing works
Influenza-Specific T Cells from Older People Are Enriched in the Late Effector Subset and Their Presence Inversely Correlates with Vaccine Response
Wagar, L. E., Gentleman, B., Pircher, H., McElhaney, J. E., & Watts, T. H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023698 · Cited by 42 · see citing works
Chronic Hepatitis C Virus Infection in Older Adults
High, K. P., Marcus, E., & Tur‐Kaspa, R. (2005) · Clinical Infectious Diseases · doi:10.1086/497597 · Cited by 40 · see citing works
Cytomegalovirus, aging, and HIV: a perfect storm.
Barrett, L., Fowke, K. R., & Grant (2012) · PubMed · Cited by 40 · see citing works
NKG2C+CD57+Natural Killer Cell Expansion Parallels Cytomegalovirus-Specific CD8+T Cell Evolution towards Senescence
Heath, J., Newhook, N., Comeau, E. M., Gallant, M., Fudge, N. J., & Grant, M. D. (2016) · Journal of Immunology Research · doi:10.1155/2016/7470124 · Cited by 40 · see citing works
Immunosénescence et infections, mythe ou réalité ?
Crétel, E., Veen, I. D. G.-V., Pierrès, A., Bongrand, P., & Gavazzi, G. (2010) · Médecine et Maladies Infectieuses · doi:10.1016/j.medmal.2009.12.008 · Cited by 38 · see citing works
Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
Vitamin D and the Immune System from the Nephrologist's Viewpoint
Lang, C.-L., Wang, M., Chiang, C., & Lu, K. (2014) · ISRN Endocrinology · doi:10.1155/2014/105456 · Cited by 37 · see citing works
Immunotherapy with Listeria reduces metastatic breast cancer in young and old mice through different mechanisms
Jahangir, A., Chandra, D., Quispe‐Tintaya, W., Singh, M., Selvanesan, B. C., & Gravekamp, C. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1342025 · Cited by 35 · see citing works
The balance between influenza- and RSV-specific CD4 T cells secreting IL-10 or IFNγ in young and healthy-elderly subjects
Lee, F. E.-H., Walsh, E. E., Falsey, A. R., Liu, N., Liu, D., Divekar, A., Snyder-Cappione, J. E., & Mosmann, T. R. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.06.011 · Cited by 34 · see citing works
Dietary folate improves age-related decreases in lymphocyte function
Field, C. J., Aerde, A. V., Drager, K., Goruk, S., & Basu, T. K. (2005) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2005.04.010 · Cited by 34 · see citing works
HIV infection and aging of the innate immune system
Hearps, A. C., Angelovich, T. A., Jaworowski, A., MILLS, J. S., LANDAY, A. L., & Crowe, S. M. (2011) · Sexual Health · doi:10.1071/sh11028 · Cited by 33 · see citing works
Systemic hypoxia promotes lymphocyte apoptosis induced by oxidative stress during moderate exercise
Wang, J.-S., & Lin, C.-T. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1231-2 · Cited by 29 · see citing works
Respiratory Syncytial Virus Infections in the Adult Asthmatic – Mechanisms of Host Susceptibility and Viral Subversion
Westerly, B. D., & Peebles, R. S. (2010) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2010.08.006 · Cited by 29 · see citing works
Distinct aging profiles of CD8+ T cells in blood versus gastrointestinal mucosal compartments
Dock, J., Ramirez, C. M., Hultin, L. E., Hausner, M. A., Hultin, P. M., Elliott, J. E., Yang, O. O., Anton, P. A., Jamieson, B. D., & Effros, R. B. (2017) · PLoS ONE · doi:10.1371/journal.pone.0182498 · Cited by 29 · see citing works
Self-citation
Aging- and Tumor-Mediated Increase in CD8+CD28− T Cells Might Impose a Strong Barrier to Success of Immunotherapy in Glioblastoma
Huff, W. X., Bam, M., Shireman, J. M., Kwon, J. H., Song, L., Newman, S., Cohen‐Gadol, A., Shapiro, S., Jones, T., Fulton, K., et al. (2021) · ImmunoHorizons · doi:10.4049/immunohorizons.2100008 · Cited by 28 · see citing works
GM‐CSF and IL ‐7 fusion cytokine engineered tumor vaccine generates long‐term Th‐17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma
Shireman, J. M., Gonugunta, N., Zhao, L., Pattnaik, A., Distler, E., Her, S., Wang, X., Das, R., Galipeau, J., & Dey, M. (2023) · Aging Cell · doi:10.1111/acel.13864 · Cited by 26 · see citing works
Chronic alcohol increases CD8+ T-cell immunosenescence in simian immunodeficiency virus-infected rhesus macaques
Katz, P. S., Siggins, R. W., Porretta, C., Armstrong, M. L., Zea, A. H., Mercante, D. E., Parsons, C. H., Veazey, R. S., Bagby, G. J., Nelson, S., et al. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.09.003 · Cited by 25 · see citing works
Survival and Proliferation of CD28- T Cells During HIV-1 Infection Relate to the Amplitude of Viral Replication
Vivar, N., Ruffin, N., Sammicheli, S., Hejdeman, B., Réthi, B., & Chiodi, F. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir156 · Cited by 25 · see citing works
CD28null T cells in aging and diseases: From biology to assessment and intervention
Guan, Y., Cao, M., Wu, X., Yan, J., Hao, Y., & Zhang, C. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.111807 · Cited by 26 · see citing works
Do Membrane Rafts Contribute to Human Immunosenescence?
Tomoiu, A., Larbi, A., Fortin, C. F., Dupuis, G., & Fülöp, T. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1395.008 · Cited by 24 · see citing works
Cancer vaccines in old age
Gravekamp, C. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.009 · Cited by 20 · see citing works
Significant IFNγ responses of CD8+ T cells in CMV-seropositive individuals with autoimmune arthritis
Almanzar, G., Schmalzing, M., Trippen, R., Höfner, K., Weißbrich, B., Geissinger, E., Meyer, T., Liese, J. G., Tony, H., & Prelog, M. (2016) · Journal of Clinical Virology · doi:10.1016/j.jcv.2016.02.010 · Cited by 18 · see citing works
How Does Cellular Senescence Prevent Cancer?
Lynch, M. (2006) · DNA and Cell Biology · doi:10.1089/dna.2006.25.69 · Cited by 18 · see citing works
The importance of the age factor in cancer vaccination at older age
Gravekamp, C. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0683-x · Cited by 17 · see citing works
HIV-1 Infection and the Aging of the Immune System: Facts, Similarities and Perspectives
Biasi, S. D., Pinti, M., Nasi, M., Gibellini, L., Bertoncelli, L., Manzini, S., Mussini, C., & Cossarizza, A. (2011) · Journal of Experimental & Clinical Medicine · doi:10.1016/j.jecm.2011.06.001 · Cited by 17 · see citing works
The impact of aging on cancer vaccination
Gravekamp, C. (2011) · Current Opinion in Immunology · doi:10.1016/j.coi.2011.05.003 · Cited by 17 · see citing works
Prognostic effect of Ki-67 expression in rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone-treated diffuse large B-cell lymphoma is limited to non-germinal center B-cell-like subtype in late-elderly patients
Koh, Y. W., Hwang, H. S., Park, C.-S., Yoon, D. H., Suh, C., & Huh, J. (2015) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2015.1004169 · Cited by 16 · see citing works
Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence
Meijers, R. W. J., Dzierżanowska‐Fangrat, K., Zborowska, M., Solarska, I., Tielemans, D., van Turnhout, B. A. C., Driessen, G. J. A., van der Burg, M., van Dongen, J. J. M., Chrzańowska, K., et al. (2016) · Journal of Clinical Immunology · doi:10.1007/s10875-016-0363-5 · Cited by 15 · see citing works
Metabolic and senescence characteristics associated with the immune microenvironment in ovarian cancer
Xiong, J., Fu, Y., Huang, J., Wang, Y., Jin, X., Wan, X., Huang, L., & Huang, Z. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1265525 · Cited by 14 · see citing works
Characterization of KIR + NKG2A + Eomes− NK‐like CD8+ T cells and their decline with age in healthy individuals
Kasakovski, D., Zeng, X., Lai, J., Yu, Z. H., Yao, D., Chen, S., Zha, X., Li, Y., & Xu, L. (2020) · Cytometry Part B Clinical Cytometry · doi:10.1002/cyto.b.21945 · Cited by 14 · see citing works
The Benefit of Anti-Inflammatory and Renal-Protective Dietary Ingredients on the Biological Processes of Aging in the Kidney
Panickar, K. S., & Jewell, D. E. (2018) · Biology · doi:10.3390/biology7040045 · Cited by 13 · see citing works
Aging and Cancer Vaccines
Gravekamp, C., & Chandra, D. (2013) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2013010588 · Cited by 12 · see citing works
Cancer vaccination: Manipulation of immune responses at old age
Gravekamp, C., Kim, S. H., & Castro, F. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.05.003 · Cited by 12 · see citing works
T-cell and B-cell perturbations identify distinct differences in HIV-2 compared with HIV-1-induced immunodeficiency
Hønge, B. L., Petersen, M. S., Jespersen, S., Medina, C., Te, D., Kjerulff, B. D., Engell-Sørensen, T., Madsen, T. V., Laursen, A. L., Wejse, C. M., et al. (2019) · AIDS · doi:10.1097/qad.0000000000002184 · Cited by 11 · see citing works
Altered molecular repertoire of immune system by renal dysfunction in the elderly: is prediction and targeted prevention in the horizon?
Lang, C.-L., Wang, M., Hung, K., Chiang, C., & Lu, K. (2013) · The EPMA Journal · doi:10.1186/1878-5085-4-17 · Cited by 11 · see citing works
A Review of Chronic Kidney Disease and the Immune System: A Special Form of Immunosenescence
Lang, C.-L. (2014) · Journal of Gerontology & Geriatric Research · doi:10.4172/2167-7182.1000144 · Cited by 10 · see citing works
Mechanisms of Estrogen Action in Bone
Pacifici, R. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00059-8 · Cited by 9 · see citing works
Is cancer vaccination feasible at older age?
Gravekamp, C., & Jahangir, A. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.025 · Cited by 8 · see citing works
Osteoporosis, Inflammation and Ageing
Ginaldi, L., Mengoli, L. P., & Martinis, M. D. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_64 · Cited by 8 · see citing works
Osteobiology of Aging
Chandra, A., Rosenzweig, A. B., & Pignolo, R. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-72228-3_1 · Cited by 6 · see citing works
Whole-body interdiction of lengthening of telomeres: a proposal for cancer prevention
J., D. (2005) · Frontiers in bioscience · doi:10.2741/1707 · Cited by 7 · see citing works
Overview
Lorenzo, J. A., Choi, Y., Horowitz, M. C., & Takayanagi, H. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-375670-1.10001-9 · Cited by 6 · see citing works
Osteoporosis, Inflammation, and Aging
Ginaldi, L., Mengoli, L. P., Sirufo, M. M., & Martinis, M. D. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_64 · Cited by 6 · see citing works
Immunity: It’s in Our Bones
Woodland, D. L., & Blackman, M. A. (2005) · Immunity · doi:10.1016/j.immuni.2005.02.002 · Cited by 5 · see citing works
The role of CD8+ T cells in the immunoregulation of osteoporosis
Chen, Z., Hu, H., Hu, D., Du, Q., Yang, H. U. I., Xu, R., Yu, P., Hu, X., & Hu, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1874242 · Cited by 4 · see citing works
Effects of Fermented Soybean Paste Chungkukjang on the Immunoreactivity in Ovariectomized Mice
Park, H., Yoon, L., & Kim, H. (2013) · Journal of the Korean Society of Food Science and Nutrition · doi:10.3746/jkfn.2013.42.12.1930 · Cited by 4 · see citing works
The Role of the Immune System in the Development of Osteoporosis
Mödder, U. I., Riggs, B. L., & Khosla, S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-375670-1.10009-3 · Cited by 4 · see citing works
Ergebnisse aus der biomedizinischen Alternsforschung
Pfister, G., Herndler‐Brandstetter, D., & Grubeck-Loebenstein, B. (2006) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-006-1278-8 · Cited by 4 · see citing works
Review on immunosenescence
Ginaldi, L., Mengoli, L. P., & Martinis, M. D. (2007) · Reviews in Clinical Gerontology · doi:10.1017/s0959259808002487 · Cited by 4 · see citing works
Osteoporosis – an immune mediated disease?
Martinis, M. D., Mengoli, L. P., & Ginaldi, L. (2007) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2007.09.001 · Cited by 4 · see citing works
From Inflamm-Aging to Immunosenescence
Fülöp, T., Witkowski, J. M., Cohen, A. A., Dupuis, G., Hirokawa, K., & Larbi, A. (2019) · Cambridge University Press eBooks · doi:10.1017/9781316677018.006 · Cited by 3 · see citing works
Osteobiology of Aging
Rosenzweig, A. B., & Pignolo, R. J. (2010) · Humana Press eBooks · doi:10.1007/978-1-60327-467-8_1 · Cited by 3 · see citing works
Role of Immunosenescence in Infections and Sepsis in the Elderly
Fülöp, T., Castle, S. C., Larbi, A., Fortin, C. F., Lesur, O., & Pawelec, G. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_48 · Cited by 3 · see citing works
Senescencia del sistema inmune y alteraciones relacionadas con el asma
Vega-Robledo, G. B., & Rico-Rosillo, M. G. (2017) · Revista Alergia México · doi:10.29262/ram.v64i2.264 · Cited by 3 · see citing works
The senescence-inhibitory p53 isoform Δ133p53α: enhancing cancer immunotherapy and exploring novel therapeutic approaches for senescence-associated diseases
Nakamichi, S., Yamada, L., Roselle, C., Horikawa, I., June, C. H., & Harris, C. C. (2025) · GeroScience · doi:10.1007/s11357-025-01819-y · Cited by 2 · see citing works
T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy
van den Broecke, L., der Vreken, A. V., Watté, F., Meeus, F., Veirman, K. D., Breckpot, K., Bruyne, E. D., & Menu, E. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02923-x · Cited by 3 · see citing works
T-Cell Signalling, a Complex Process for T-Cell Activation Compromised with Aging: When Membrane Rafts Can Simplify Everything
Fülöp, T., Pawelec, G., Fortin, C. F., & Larbi, A. (2008) · Springer eBooks · doi:10.1007/978-0-387-76842-7_6 · Cited by 2 · see citing works
Immunity and Nutrition
Trinh, C. (2007) · Nutrition and disease prevention · doi:10.1201/9781420005493.ch6 · Cited by 2 · see citing works
Osteoporosis, Inflammation, and Aging
Ginaldi, L., Mengoli, L. P., Sirufo, M. M., & Massimo, D. M. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_64-1 · Cited by 2 · see citing works
Immunosenescence Modulation by Vaccination
McElhaney, J. E. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_71 · Cited by 2 · see citing works
Role of Immunosenescence in Infections and Sepsis in the Elderly
Lesur, O., Fülöp, T., Castle, S. C., Larbi, A., Fortin, C. F., & Pawelec, G. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_48 · Cited by 2 · see citing works
Immunology of Osteoporosis
Kerschan‐Schindl, K., Nebot, E., & Pietschmann, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_153-1 · Cited by 2 · see citing works

The role of CD8<sup>+</sup> T‐cell replicative senescence in human aging
Effros, R. B., Dagarag, M., Spaulding, C., & Man, J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00259.x · Cited by 336 · see citing works
Self-citation
Correspondence to:
Effros, R. B., Dagarag, M., Spaulding, C., Man, J. Y., Effros, R. B., Dagarag, M., Spaulding, C., & Effros, R. B. (2014)
Self-citation
T Cell Replicative Senescence Pleiotropic Effects on Human Aging
Effros, R. B. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1297.022 · Cited by 33 · see citing works
Self-citation
T Cell Replicative Senescence in Human Aging
P. Chou, J., & B. Effros, R. (2013) · Current Pharmaceutical Design · doi:10.2174/138161213805219711 · Cited by 323 · see citing works
Self-citation
Senescent CD8 T effector memory cells are functionally impaired, enriched in aging and disease, and a barrier to immunotherapy
Turano, P. S., Akbulut, E., Aquino, N. M., Garza-Martínez, L., Singh, S., Aviv, A., Toupance, S., Yap, G. S., Fitzgerald-Bocarsly, P., Martínez-Zamudio, R. I., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.64898/2025.12.16.694716 · Cited by 2 · see citing works

Authors: Effros, R. B.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Effros, Rita B.
ORCID: Effros, Rita B.
Venue: Experimental Gerontology
Publisher: Elsevier BV
Published: 2004-04
Volume: 39
Issue: 4
Pages: 517-524
ISSN: 0531-5565 (ISSN-L)
DOI: 10.1016/j.exger.2003.09.024
OpenAlex: W2006184746
Cited by: 127
References: 85
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 9 · 2018: 10 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 4
FWCI: 5.76
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Gerontology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r21ai047665-02)
National Institute on Aging (AG-10415, P60AG010415)
National Institute of Allergy and Infectious Diseases (AI47665)
Topics: Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: replicative senescence, CD8+ T cells, human aging, telomere shortening, cell cycle arrest, apoptosis resistance, memory T cells, influenza vaccine response, bone homeostasis, osteoporosis, osteoporotic fractures, cytokines, immunosenescence
MeSH terms: Aging, Estrogens, Humans, Bone Remodeling, Cellular Senescence, CD8-Positive T-Lymphocytes

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

Replicative senescence of CD8 T cells: Effect on human ageing

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks