The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Decline in CD28+ T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence
Abstract
The dramatic decline in immune function with age, especially in T cell proliferative activity, has been documented extensively in experimental animal models and in clinical studies of the elderly. A similar proliferative decline is also seen in long-term T lymphocyte cultures used to study in vitro cellular senescence. We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor. Our analysis shows a significant decrease (p < 0.001) in the percentage of T cells expressing CD28 in the elderly cohort, with values ranging from 44% to 90%, as compared to the mean control value of 91%. The decline in the percentage of CD28+ T cells correlates with a reduction in the CD4/CD8 ratio (r2 = 0.695, p < 0.0001). Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age." The concordance of proliferative decline and loss of CD28 in the centenarians and in the in vitro cultures suggest that a Hayflick phenomenon may operate in vivo leading to immunosenescence.
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“These T cells do not express the co-stimulatory molecule CD28, required for the activation of T cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“The loss of CD28 occurs following cell proliferation, according to the observation that the CD28− T cells have shorter telomeres than CD28+ cells.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“Late-stage memory senescent T-cells may also acquire new functions, such as suppressive activity, as demonstrated in vitro.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“CD28 seems a good biomarker of immunosenescence, as further suggested by findings that late-differentiated CD8+/CD28− T cells tend to accumulate particularly in older people, frail or affected by age-related diseases.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
In the citing paper
“In addition, they are producers of pro-inflammatory cytokines (17, 18, 41–47).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [41]
Citations
Cites
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
Differential T Cell Costimulatory Requirements in CD28-Deficient Mice
Shahinian, A., Pfeffer, K., Lee, K. P., Kündig, T. M., Kishihara, K., Wakeham, A. C., Kawai, K., Ohashi, P. S., Thompson, C. B., & Mak, T. W. (1993) · Science · doi:10.1126/science.7688139 · Cited by 1,264
Tumor Rejection After Direct Costimulation of CD8 + T Cells by B7-Transfected Melanoma Cells
Townsend, S. E., & Allison, J. P. (1993) · Science · doi:10.1126/science.7678351 · Cited by 1,139
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
June, C. H., Ledbetter, J. A., Gillespie, M., Lindsten, T., & Thompson, C. B. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.12.4472-4481.1987 · Cited by 565
CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells
Jenkins, M. K., Taylor, P., Norton, S. D., & Urdahl, K. B. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.147.8.2461 · Cited by 561
Tan, P., Anasetti, C., Hansen, J. A., Melrose, J. E., Brunvand, M. W., Bradshaw, J., Ledbetter, J. A., & Linsley, P. S. (1993) · The Journal of Experimental Medicine · doi:10.1084/jem.177.1.165 · Cited by 461
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
Liu, Y., & Janeway, C. A. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.172.6.1735 · Cited by 361
The Cellular and Subcellular Bases of Immunosenescence
Thoman, M. L., & Weigle, W. O. (1989) · Advances in immunology · doi:10.1016/s0065-2776(08)60655-0 · Cited by 318
Research works printed but not linked: 2
- June, 1987, T cell interleukin 2 gene expression, Molec. Cell Biol., 7, 4472, 10.1128/MCB.7.12.4472 · DOI
- Murasko, 1988, Association of lack of mitogen induced proliferation with increased mortality in the elderly, Aging: Immunology & Infectious Disease, 1, 1
Cited by
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Heron, M., Claessen, A. M. E., Grutters, J. C., & van den Bosch, J. M. M. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.04076.x · Cited by 29
Amu, S., Lantto, R., Bekele, Y., Nasi, A., Bengtsson, C., Réthi, B., Sorial, S., Meini, G., Zazzi, M., Hejdeman, B., et al. (2016) · Medicine · doi:10.1097/md.0000000000003738 · Cited by 29
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Berg, M., & Zavazava, N. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0107065 · Cited by 29
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“Increased numbers of CD28-and CD27-T-cells are observed in the elderly [41,42].”
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Verdecia, B. G., Hernández, D. S., Lorenzo-Luaces, P., Badia, T., Rupalé, I. L., Mazorra, Z., Crombet, T., & Dávila, A. L. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-16 · Cited by 27
“Discussion Changes in cells of the immune system related to age have been the subject of many studies in the last two decades [18-22].”
BackgroundImmunosenescence in the nursing home elderly
Johnstone, J., Millar, J., Lelic, A., Verschoor, C. P., Walter, S. D., Devereaux, P. J., Bramson, J. L., & Loeb, M. B. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-50 · Cited by 27
Vidric, M., Suh, W., Dianzani, U., Mak, T. W., & Watts, T. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.11.7288 · Cited by 27
Dawson, H. D., & Ross, A. C. (1999) · Journal of Nutrition · doi:10.1093/jn/129.10.1782 · Cited by 27
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Anderko, R. R., & Mailliard, R. B. (2023) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiac007 · Cited by 28
Whisler, R. L., Karanfilov, C. I., Newhouse, Y. G., Fox, C. C., Lakshmanan, R. R., & Beiqing, L. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00084-0 · Cited by 26
A challenge for the future: aging and HIV infection
Rickabaugh, T. M., & Jamieson, B. D. (2010) · Immunologic Research · doi:10.1007/s12026-010-8167-9 · Cited by 26
“loss of CD28 on T-cells is the most significant genetic and phenotypic change correlated with replicative senescence [62] and that clonal expansions of CD28CD8 T cells are used clinically to predict mortality risk in the elderly [62, 63].”
BackgroundVivar, 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
“that have undergone chronic antigen-specific activation in HIV-1–infected patients [9–11], in aged individuals [12], and in patients with diverse autoimmune diseases [13, 14].”
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Nabeshima, S., Murata, M., Kikuchi, K., Ikematsu, H., Kashiwagi, S., & Hayashi, J. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01819.x · Cited by 25
Mogford, J. E., Liu, W. R., Reid, R. R., Chiu, C., Said, H. K., Chen, S.-J., Harley, C. B., & Mustoe, T. A. (2006) · Human Gene Therapy · doi:10.1089/hum.2006.17.651 · Cited by 26
Activated T Lymphocytes Disappear from Circulation during Endotoxemia in Humans
Krabbe, K. S., Brüünsgaard, H., Qvist, J., Fonsmark, L., Møller, K., Hansen, C. M., Skinhøj, P., & Pedersen, B. K. (2002) · Clinical and Vaccine Immunology · doi:10.1128/cdli.9.3.731-735.2002 · Cited by 25
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BackgroundPawelec, G., Mariani, E., Bradley, B., & Solana, R. (2000) · Biogerontology · doi:10.1023/a:1010086229931 · Cited by 25
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Kouli, A., & Williams-Gray, C. H. (2022) · Journal of Parkinson's Disease · doi:10.3233/jpd-223228 · Cited by 20
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 27
Connoy, A., Trader, M., & High, K. P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.11.003 · Cited by 24
Naismith, E., & Pangrazzi, L. (2019) · Bioscience Reports · doi:10.1042/bsr20190371 · Cited by 24
Molecular and Cellular Aspects of Macrophage Aging
Sebastián, C., Lloberas, J., & Celada, A. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_46 · Cited by 24
4-1BBL costimulation retrieves CD28 expression in activated T cells
Habibagahi, M., Jaberipour, M., & Searle, P. F. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.01.003 · Cited by 24
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von Zglinicki, T., Martin-Ruiz, C. M., & Saretzki, G. C. (2005) · Signal Transduction · doi:10.1002/sita.200400049 · Cited by 23
Apoptosis and reduced influenza A virus specific CD8+ T cells in aging mice
Zhang, Y., Wang, Y., Gilmore, X., Xu, K., Chen, M., Tebebi, P., & Mbawuike, I. N. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401011 · Cited by 23
Immunological and immunogenetic markers of successful and unsuccessful ageing
Candore, G., Colonna‐Romano, G., Lio, D., & Caruso, C. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)13003-3 · Cited by 23
Increased expression of PD 1 and CD 39 on CD 3+CD 4+ skin T cells in the elderly
Zuelgaray, E., Boccara, D., Ly Ka So, S., Boismal, F., Mimoun, M., Bagot, M., Bensussan, A., Bouaziz, J., & Michel, L. (2019) · Experimental Dermatology · doi:10.1111/exd.13842 · Cited by 23
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Immunosenescence and age-related immune cells: causes of age-related diseases
Kim, N., Sim, S.-J., Han, H.-G., Yoon, J.-H., & Han, Y. (2024) · Archives of Pharmacal Research · doi:10.1007/s12272-024-01529-7 · Cited by 22
“The accumulation of these cells, primarily driven by TCR stimulation, manifests with a memory T cell phenotype and tends to be increased further with advancing age (Effros et al. 1994; Fagnoni et al. 1996).”
Tortorella, C., Loria, M. P., Piazzolla, G., Schulze‐Koops, H., Lipsky, P. E., Jirillo, E., & Antonaci, S. (1997) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(97)00033-2 · Cited by 21
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Cavanagh, M., Qi, Q., Weyand, C. M., & Goronzy, J. J. (2011) · Europe PMC (PubMed Central) · Cited by 20
Saretzki, G. C., & von Zglinicki, T. (1999) · Zeitschrift für Gerontologie und Geriatrie · doi:10.1007/s003910050086 · Cited by 20
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Jensen, K. Y., Jacobsen, M., Schrøder, H. D., Aagaard, P., Nielsen, J. L., Jørgensen, A. N., Boyle, E., Bech, R. D., Rosmark, S., Diederichsen, L. P., et al. (2019) · Arthritis Research & Therapy · doi:10.1186/s13075-019-2036-2 · Cited by 21
Neuber, K., Schmidt, S., & Mensch, A. (2003) · Immunology · doi:10.1046/j.1365-2567.2003.01640.x · Cited by 19
Justice, A. C., & Whalen, C. C. (1996) · Journal of General Internal Medicine · doi:10.1007/bf02599036 · Cited by 19
Caruso, C., & Vasto, S. (2016) · Encyclopedia of Immunobiology · doi:10.1016/b978-0-12-374279-7.19003-4 · Cited by 18
Predicting Cytotoxic T-cell Age from Multivariate Analysis of Static and Dynamic Biomarkers
Rivet, C. A., Hill, A. S., Lu, H., & Kemp, M. L. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.003921 · Cited by 18
Johnson, J. E., McNeil, L. K., Megati, S., Witko, S. E., Roopchand, V., Obregon, J., Illenberger, D. M., Kotash, C. S., Nowak, R. M., Braunstein, E., et al. (2012) · Immunology Letters · doi:10.1016/j.imlet.2012.12.005 · Cited by 18
Brzezińska, A., Magalska, A., & Sikora, E. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00012-5 · Cited by 18
Alberro, A., Osorio-Querejeta, I., Sepúlveda, L., Fernández‐Eulate, G., Mateo‐Abad, M., Muñoz‐Culla, M., Carregal‐Romero, S., Matheu, A., Vergara, I., de Munaín, A. L., et al. (2019) · Aging · doi:10.18632/aging.102517 · Cited by 21
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BackgroundSiwicki, J. K., Hedberg, Y., Nowak, R., Lodén, M., Zhao, J., Landberg, G., & Roos, G. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00088-7 · Cited by 18
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Schmoranzer, F., Fuchs, N., Markolin, G., Carlin, E., Sakr, L., & Sommeregger, U. (2009) · International Journal for Vitamin and Nutrition Research · doi:10.1024/0300-9831.79.56.308 · Cited by 17
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BackgroundInmunosenescencia: el rol de la edad en la esclerosis múltiple
Ostolaza, A., Laviñeta, J. C., & Blanco, T. A. (2020) · Neurología · doi:10.1016/j.nrl.2020.05.016 · Cited by 17
Behrens, N. E., Wertheimer, A. M., Klotz, S. A., & Ahmad, N. (2018) · PLoS ONE · doi:10.1371/journal.pone.0199101 · Cited by 16
Gupta, S., Su, H., Agrawal, S., & Gollapudi, S. V. S. (2018) · Immunity & Ageing · doi:10.1186/s12979-017-0109-0 · Cited by 16
Tc1/Tc2 ratio in the inflammatory process in patients with Behçet′s disease
Houman, H., Hamzaoui, A., Ghorbal, I. B., Khanfir, M. S., Feki, M., & Hamzaoui, K. (2004) · Mediators of Inflammation · doi:10.1080/09629350400003167 · Cited by 17
Centenarians and the Genetics of Longevity
Perls, T. T., Terry, D. F., Silver, M. H., Shea-Drinkwater, M., Bowen, J., Joyce, E., Ridge, S. B., Fretts, R. C., Daly, M. J., Brewster, S. J., et al. (2000) · Results and problems in cell differentiation · doi:10.1007/978-3-540-48003-7_1 · Cited by 17
“1998), immune function (Mariotti et al. 1992; Effros et al. 1994; Francheschi et al. 1995), blood c10tting (Mari et al.”
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Franzese, O., Barbaccia, M. L., Bonmassar, E., & Graziani, G. (2018) · Chemotherapy · doi:10.1159/000487534 · Cited by 17
Proliferation and apoptosis of human T cells during replicative senescence--a critical approach.
Jaruga, E., Skierski, J., Radziszewska, E., & Sikora, E. (2000) · Acta Biochimica Polonica · doi:10.18388/abp.2000_4009 · Cited by 16
Expansions of CD8CD28− and CD8TcRVβ5.2 T Cells in Peripheral Blood of Heavy Alcohol Drinkers
Arosa, F. A., Porto, G., Cabeda, J. M., Lacerda, R., Resende, D., Cruz, E., Cardoso, C. S. D. F. L. P., Fonseca, M., Simões, C. R. B., Rodrigues, P., et al. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02020.x · Cited by 16
Wick, G., & Grubeck‐Loebenstein, B. (1997) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(97)00025-6 · Cited by 16
The Role of Aging and Senescence in Immune Checkpoint Inhibitor Response and Toxicity
Jain, S. S., Sojo, G. B., Sun, H., Friedland, B. N., McNamara, M. E., Schmidt, M. O., & Wellstein, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137013 · Cited by 17
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BackgroundMethodNew methodologies in ageing research
Osborne, B., Bakula, D., Ezra, M. B., Dresen, C., Hartmann, E., Kristensen, S. M., Mkrtchyan, G. V., Nielsen, M. H., Petr, M. A., & Scheibye‐Knudsen, M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101094 · Cited by 18
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Kim, B. B., Lyons, T. M., Parada, J. P., Uphold, C. R., Yarnold, P. R., Hounshell, J. B., Sipler, A. M., Goetz, M. B., DeHovitz, J. A., Weinstein, R. A., et al. (2001) · Journal of General Internal Medicine · doi:10.1046/j.1525-1497.2001.016009583.x · Cited by 15
Shankar, E. M. (2015) · World Journal of Virology · doi:10.5501/wjv.v4.i1.17 · Cited by 15
My T's gone cold, I'm wondering why...
Aspinall, R., Henson, S. M., & Pido-Lopez, J. (2003) · Nature Immunology · doi:10.1038/ni0303-203 · Cited by 15
Okba, A. M., Raafat, M. A. E. R., Farres, M. N., Melek, N. A. E. N., Amin, M. M., & Gendy, N. N. (2019) · Human Immunology · doi:10.1016/j.humimm.2019.03.008 · Cited by 14
Jalilian, B., Christiansen, S. H., Einarsson, H. B., Pirozyan, M. R., Petersen, E., & Vorup‐Jensen, T. (2013) · Molecular and Cellular Therapies · doi:10.1186/2052-8426-1-2 · Cited by 13
The influence of intrinsic and extrinsic factors on immune system aging
Badowski, M., Shultz, C. L., Eason, Y., Ahmad, N., & Harris, D. T. (2014) · Immunobiology · doi:10.1016/j.imbio.2014.02.008 · Cited by 13
Centenarians: Health and Frailty
Forette, B. (1997) · Springer eBooks · doi:10.1007/978-3-642-60813-1_7 · Cited by 12
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Perls, T. T., & Puca, A. A. (2002) · Pharmacogenomics · doi:10.1517/14622416.3.4.469 · Cited by 11
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Baker, G. T., & Martin, G. R. (1997) · Springer eBooks · doi:10.1007/978-1-4757-2705-0_1 · Cited by 11
Leposavić, G., Pilipović, I., & Nanut, M. P. (2011) · NeuroImmunoModulation · doi:10.1159/000329499 · Cited by 11
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LUPIEN, S. J., & Wan, N. (2005) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780198567523.003.0004 · Cited by 10
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Tarazona, R., DelaRosa, O., Peralbo, E., Peña, J., Solana, R., & Sofía, R. (2003) · Cited by 10
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Plunkett, F. J., Soares, M. V. D., Salmon, M., & Akbar, A. N. (2000) · APOPTOSIS · doi:10.1023/a:1009672331030 · Cited by 10
Telomerase: is it the future diagnostic and prognostic tool in human cancer?
Mabruk, M. J. E. M. F., & O’Flatharta, C. (2005) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.5.6.907 · Cited by 10
Kottilil, S., Gamberg, J., Bowmer, I., Trahey, J., Howley, C., Gallant, M., & Grant, M. D. (2000) · Journal of Clinical Immunology · doi:10.1023/a:1006633429087 · Cited by 10
Li, L., Yu, F., Yang, S., Li, H., Tang, Y., & Ma, C. (2025) · BMC Infectious Diseases · doi:10.1186/s12879-025-10511-7 · Cited by 10
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da Silva, P. H. L., de Castro, K. K. G., Mendes, M. A., Leal-Calvo, T., Leal, J. M. P., Nery, J. A. D. C., Sarno, E. N., Lourenço, R. A., Moraes, M. O., Lara, F. A., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.647385 · Cited by 9
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BackgroundLázničková, P., Bendíčková, K., Kepák, T., & Frič, J. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.708788 · Cited by 10
Age-related loss of immunoregulatory function in peripheral blood CD8 T cells
Crisi, G. M., Chen, L. Z., Huang, C., & Thorbecke, G. J. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00030-x · Cited by 9
Alamino, V. A., Onofrio, L. I., Acosta, C. D. V., Ferrero, P. V., Zacca, E. R., Cadile, I. I., Mussano, E. D., Onetti, L. B., Montes, C. L., Gruppi, A., et al. (2023) · European Journal of Immunology · doi:10.1002/eji.202250353 · Cited by 10
T Cell Costimulatory Molecules in Anti‐Viral Immunity: Potential Role in Immunotherapeutic Vaccines
Watts, T. H., Bertram, E. M., Bukczynski, J., & Wen, T. (2003) · Canadian Journal of Infectious Diseases and Medical Microbiology · doi:10.1155/2003/214034 · Cited by 8
“The finding that 4-1BBL can stimulate CD28–T cells is relevant to the human immune response because, in contrast to mice, humans accumulate CD28–CD8+ T cells with age (41,42).”
BackgroundBenito-Lopez, J. J., Marroquin-Muciño, M., Perez-Medina, M., Chavez-Dominguez, R., Aguilar‐Cázares, D., Galicia-Velasco, M., & López-González, J. S. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1101503 · Cited by 7
How‐Kit, A., Sahbatou, M., Hardy, L. M., Tessier, N. P., Schiavon, V., Buanec, H. L., Sébaoun, J.-M., Blanché, H., Zagury, J., & Deleuze, J. (2023) · GeroScience · doi:10.1007/s11357-023-01037-4 · Cited by 6
Liaskou, E., Jeffery, L. E., Chanouzas, D., Soskic, B., Seldin, M. F., Harper, L., Sansom, D. M., & Hirschfield, G. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-07967-2 · Cited by 6
Pawelec, G. (2003) · Springer eBooks · doi:10.1007/978-94-017-0669-8_6 · Cited by 6
Death of memory T-cell subsets in humans: changes during aging
Gupta, S., & Gupta, A. (2007) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.3.4.637 · Cited by 6
Age- and Race-Related Changes in Subpopulations of Peripheral Blood Lymphocytes in Humans
Hooten, N. N., Longo, D. L., & Evans, M. K. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_85-1 · Cited by 5
Human Embryonic vs Adult Stem Cells for Transplantation Therapies
Harley, C. B., & Rao, M. S. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-423-8_13 · Cited by 5
Vendetti, S., Riccomi, A., Sacchi, A., Sciaraffia, E., Gatta, L., Pioli, C., & Magistris, M. T. D. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.10.003 · Cited by 5
Rammos, G., & Kondomerkos, D. J. (2007) · PubMed · Cited by 5
Approaches to studying costimulation of human antiviral T cell responses
Serghides, L., Vidric, M., & Watts, T. H. (2006) · Immunologic Research · doi:10.1385/ir:35:1:137 · Cited by 5
Stem Cell Senescence as the Memory of Past Injuries
Gianfranceschi, G., Gri, G., Cesselli, D., & Beltrami, A. P. (2015) · Current Pathobiology Reports · doi:10.1007/s40139-015-0071-5 · Cited by 4
“For instance, with aging, T cells increase the expression of the inhibitory molecule CTLA-4 and decrease the CD28 activator [73, 74], furthermore both CD4 and CD8 T cells acquire the expression of NK-specific KIR genes [75], and, finally, CD4 T cells can acquire cytotoxic activity through the expression of perforin an…”
BackgroundHealthy aging: when periodontal health matters
Rengo, C., Valletta, A., Liccardo, D., Spagnuolo, G., Corbi, G., Luca, F. D., Lauria, M. R., Perrotta, A., Rengo, G., Ferrara, N., et al. (2023) · Journal of Gerontology and Geriatrics · doi:10.36150/2499-6564-n580 · Cited by 5
Telomeres and the Arithmetic of Human Longevity
Aviv, A., & Bogden, J. D. (2010) · Springer eBooks · doi:10.1007/978-90-481-3999-6_18 · Cited by 4
“At this stage, they exhibit the loss of the CD28 antigen, a major immunoglobulin molecule expressed on the membrane of T lymphocytes, where it serves to amplify the T-cell receptor signal (Vallejo 2005; Effros et al. 1994 ).”
BackgroundAge, T-cell Homeostasis, and T-cell Diversity in Humans
Lamar, D. L., Weyand, C. M., & Goronzy, J. J. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_9 · Cited by 4
“A well-established feature of memory T-cell aging is the loss of the costimulatory molecule CD28 [ 64 ].”
BackgroundAging and HIV Disease: Synergistic Immunological Effects?
Effros, R. B. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_47 · Cited by 4
“These cells show permanent and irreversible loss of CD28 expression (Effros et al. 1994).”
BackgroundAn overview of the necessary thymic contributions to tolerance in transplantation
Scalea, J. R., Hickman, J. B., Moore, D. J., & Brayman, K. L. (2016) · Clinical Immunology · doi:10.1016/j.clim.2016.10.010 · Cited by 4
CD57-Expressing Lymphocytes: From Chronic Viral Response to Age-Related Inflammation
Vallejo-Bermúdez, I. M., Miranda-Echagüe, M. R., Fernández-Álvarez, S., Reina-Alfonso, I., Blanca-Pariente, L., Batista-Duharte, A., & Pera, A. (2026) · Cells · doi:10.3390/cells15050403 · Cited by 3
“The decline in CD28 expression on both CD4 + and CD8 + T lymphocytes is a well-recognized feature of immunosenescence [41].”
Petrušić, M., Stojić-Vukanić, Z., Pilipović, I., Kosec, D. J., Prijić, I., & Leposavić, G. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.112009 · Cited by 3
Rai, P., & Troen, B. R. (2011) · Springer eBooks · doi:10.1007/978-1-4419-6999-6_2 · Cited by 3
Tucker, V. C., Rye, A., Harrison, J., King, L., Duddridge, M., & Browning, M. J. (2004) · Immunobiology · doi:10.1078/0171-2985-00292 · Cited by 3
Stress and Immune System Aging
Effros, R. B. (2012) · Oxford University Press eBooks · doi:10.1093/oxfordhb/9780195394399.013.0004 · Cited by 3
Expansions of CD8CD28??? and CD8TcRV??5.2 T Cells in Peripheral Blood of Heavy Alcohol Drinkers
Arosa, F. A., Porto, G. A., Cabeda, J. M., Lacerda, R., Resende, D., Cruz, E., Cardoso, C. S. D. F. L. P., Fonseca, M., es, C. S., Rodrigues, P., et al. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200004000-00027 · Cited by 3
Metadata
- Authors
- Effros, R. B., Boucher, N., Porter, V., Zhu, X., Spaulding, C., Walford, R. L., Kronenberg, M., Cohen, D., & Schächter, F.
- Affiliations
- University of California, Los Angeles (US)
- Fondation Jean Dausset-CEPH (FR)
- Corresponding author
- Effros, Rita B.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 1994-11
- Volume
- 29
- Issue
- 6
- Pages
- 601-609
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2037915406
- Cited by
- 377
- References
- 21
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 3 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 17 · 2018: 14 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 16 · 2012: 14
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- National Institutes of Health (5r01ag005309-06)
- National Institute on Aging (AG00427, AG05309, AG-00424)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, CD28, centenarians, T cell proliferation, cellular senescence, CD4/CD8 ratio, costimulatory molecules
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cells, Cultured, Humans, Middle Aged, T-Lymphocytes, Linear Models, Case-Control Studies, T-Lymphocyte Subsets, Cellular Senescence, CD28 Antigens, Lymphocyte Count
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