CD28 Expression in T Cell Aging and Human Longevity
Abstract
Functional decrements of the immune system have a major contribution to aging and age-related diseases. Here, we further characterize the decline in proportion of CD28-positive T cells previously identified in centenarians. Cohorts of 97 centenarians, 40 subjects aged 70-90 (ELD group), and 40 young adults (under age 40) were phenotyped for T cell surface expression of CD28, CD4, and CD8 antigens. The significant decline in T cells expressing CD28 (p < 10(-4) for comparisons between adults and either ELD or centenarians) affects preferentially the CD8+ subset of T cells. This decline accounts largely for the age-related diminution of T cell responsiveness to mitogenic signals. CD28 expression is modulated in T cell cultures in a growth-related fashion and this modulation is dampened in cultures from centenarians. We propose that the decrease in CD28 expression reflects a compensatory adaptation of the immune system during aging in the face of chronic stimulation.
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Ageing changes can include reduced expression of crucial receptors such as CD28 on cytotoxic CD8+ T cells.
“These changes can include an involuted thymus235, fewer naive B and T cells236, diminished T cell receptor diversity237, higher susceptibility to T cell apoptosis238 and reduced expression of crucial receptors such as CD28 on cytotoxic CD8+ T cells239.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [239]
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“The source of these cytokines may be activated or senescent T cells, which can be identified with cellular markers [16–18].”
BackgroundPignolo, R. J. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2018.10.005 · Cited by 108 · see citing works
T cell subsets and mortality in older community-dwelling women
Semba, R. D., Margolick, J. B., Leng, S. X., Walston, J. D., Ricks, M. O., & Fried, L. P. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.09.006 · Cited by 107 · see citing works
CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28−CD8+ T Cells
Leitner, J., Herndler-Brandstetter, D., Zlabinger, G. J., Grubeck-Loebenstein, B., & Steinberger, P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1401917 · Cited by 104 · see citing works
“infants virtually all human T cells express CD28, up to 50% of the CD8 T cell compartment of elderly or chronically infected individuals are CD28(2) (8).”
BackgroundCo-stimulatory and co-inhibitory pathways in cancer immunotherapy
O’Neill, R., & Cao, X. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2019.03.003 · Cited by 101 · see citing works
“Immunotherapy—As humans age CD28 levels decrease on T cells, especially CD8+ populations, which may decrease the potential use for treatment in aging cancer populations [13].”
BackgroundLu, Y., Tan, C. T. Y., Nyunt, M. S. Z., Mok, E. W. H., Camous, X., Kared, H., Fülöp, T., Feng, L., Ng, T. P., & Larbi, A. (2016) · Oncotarget · doi:10.18632/oncotarget.8939 · Cited by 98 · see citing works
“The marked decline in CD28 expression in CD8+ T cells compared with CD4+ T cells may relate to the age-related decline in mitogeninduced T cell induction, most likely an adaptation to deal with chronic stimulation and inflammation occurring in the elderly [49].”
BackgroundCHANGES IN IMMUNE FUNCTION WITH AGE
Yung, R. L. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70151-4 · Cited by 96 · see citing works
Immunosenescence and Influenza Vaccine Efficacy
Sambhara, S. R., & McElhaney, J. E. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-540-92165-3_20 · Cited by 96 · see citing works
“1998; Sansoni et al.”
Nel, A. E., & Slaughter, N. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.124965 · Cited by 96 · see citing works
Giudice, V., Feng, X., Lin, Z., Hu, W., Zhang, F., Qiao, W., Ibanez, M. D. P. F., Rios, O., & Young, N. S. (2018) · Haematologica · doi:10.3324/haematol.2017.176701 · Cited by 92 · see citing works
“The expansion of effector memory cells could also occur in older healthy subjects as a result of lifelong exposure to common pathogens, but it is related to reduced overall immune responsiveness to novel antigens.(45,46) Consistent with previous studies, the SAA patients in our cohort had higher frequencies of CD8CD57…”
ResultVα24+ NKT cells are decreased in elderly humans
DelaRosa, O., Tarazona, R., Casado, J. G., Alonso, C., Ostos, B., Peña, J., & Solana, R. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00186-3 · Cited by 86 · see citing works
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“org Clin Cancer Res; 23(24) December 15, 2017 7475”
BackgroundInfluentialDistinct categories of immunologic changes in frail elderly
Fahey, J. L., Schnelle, J. F., Boscardin, W. J., Thomas, J. K., Gorre, M. E., Aziz, N., Sadeghi, H. M., & Nishanian, P. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00094-4 · Cited by 84 · see citing works
Helby, J., Nordestgaard, B. G., Benfield, T., & Bojesen, S. E. (2017) · Haematologica · doi:10.3324/haematol.2016.161943 · Cited by 80 · see citing works
Telomerase induction in T cells: A cure for aging and disease?
Effros, R. B. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.11.005 · Cited by 82 · see citing works
“Cross sectional analysis of T cells from different age groups has clearly documented that the proportion of cells lacking CD28 expression increases progressively with age [21].”
BackgroundSelf-citationFülöp, T., Larbi, A., Dupuis, G., & Pawelec, G. (2003) · Arthritis Research & Therapy · doi:10.1186/ar1019 · Cited by 81 · see citing works
“Indeed, experimental data clearly show that the expression of CD28 is decreasing with ageing [ 39 ].”
BackgroundFann, M., Chiu, W. K., Wood, W. H., Levine, B. L., Becker, K. G., & Weng, N. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00262.x · Cited by 81 · see citing works
“Because almost all T cells in newborn peripheral blood express CD28 (3, 12) and because the accumulation of CD28 T cells, especially in CD8þ T cells, is a gradual process with age, it has been suggested that CD28nullCD8þ T cells are derived from CD28þCD8þ T cells (13).”
BackgroundMüller, L., & Benedetto, S. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020753 · Cited by 82 · see citing works
“…Accumulation accumulation cells during these cells also undergo senescent changes later in life, with hallmarks such CD28 and the accumulation of highly differentiated effector memory T These memory for mounting advancing The proportion the balance early life, as the loss of cells [3,37,38].”
BackgroundCostimulatory mechanisms in the elderly
Effros, R. B. (2000) · Vaccine · doi:10.1016/s0264-410x(99)00503-4 · Cited by 79 · see citing works
Self-citationCaruso, C., Candore, G., Romano, G. C., Lio, D., Bonafè, M., Valensin, S., & Franceschi, C. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00255-4 · Cited by 77 · see citing works
Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes☆
Potestio, M., Pawelec, G., Lorenzo, G. D., Candore, G., D’Anna, C., Gervasi, F., Lio, D., Tranchida, G., Caruso, C., & Romano, G. C. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00041-8 · Cited by 76 · see citing works
Late onset systemic lupus erythematosus: no substantial differences using different cut-off ages
J, M. P. J., Govoni, M., Castellino, G., Rizzo, N., Fotinidi, M., & Trotta, F. (2006) · Rheumatology International · doi:10.1007/s00296-006-0284-3 · Cited by 74 · see citing works
Rizzo, L. B., Do Prado, C. H., Grassi-Oliveira, R., Wieck, A., Correa, B. L., Teixeira, A. L., & Bauer, M. E. (2013) · Bipolar Disorders · doi:10.1111/bdi.12121 · Cited by 73 · see citing works
Jeune, B. (2002) · Aging Clinical and Experimental Research · doi:10.1007/bf03324421 · Cited by 76 · see citing works
Bryl, E., & Witkowski, J. M. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.10.029 · Cited by 73 · see citing works
Schwaiger, S., Wolf, A. M., Robatscher, P., Jenewein, B., & Grubeck‐Loebenstein, B. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.1.613 · Cited by 73 · see citing works
“Whether the increase in CD8 CD28 IFN- -producing T cells characteristically observed in healthy elderly persons (48, 49) is also a symptom of underlying latent CMV infection is still a matter of debate (50, 51).”
BackgroundDecman, V., Laidlaw, B. J., DiMenna, L. J., Abdulla, S., Mozdzanowska, K., Erikson, J., Ertl, H. C. J., & Wherry, E. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902063 · Cited by 71 · see citing works
Aging and the immune response to organ transplantation
Colvin, M. M., Smith, C. A., Tullius, S. G., & Goldstein, D. R. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90601 · Cited by 72 · see citing works
“Most studies have focused on adaptive immunity — in particular, T cell function — with several reports showing that aging impairs T cell IL-2 production and Th1 immunity (62–64), CD28 signaling (65), and immune synapse formation (66).”
BackgroundEarly Priming Minimizes the Age-Related Immune Compromise of CD8+ T Cell Diversity and Function
Valkenburg, S., Venturi, V., Dang, T. H. Y., Bird, N. L., Doherty, P. C., Turner, S. J., Davenport, M. P., & Kedzierska, K. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002544 · Cited by 69 · see citing works
“Ageing can also be associated with abnormal cellular functions such as distorted cytokine secretion (IL-2, IL-4 and IFN-c) profiles [15–17], decreased granzyme B production [18,19] and reduced proliferative capacity due to the loss of CD28 expression [20].”
BackgroundEffects of Aging on Immune Function
Stowe, R. P., & Goodwin, J. S. (2011) · Springer eBooks · doi:10.1007/978-1-4419-6999-6_4 · Cited by 68 · see citing works
Genetic alterations in the ageing immune system: impact on infection and cancer
Effros, R. B. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00171-9 · Cited by 67 · see citing works
Self-citationIn vitro senescence of immune cells
Effros, R. B., Dagarag, M. D., & Valenzuela, H. (2003) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.004 · Cited by 62 · see citing works
Self-citationFrom Hayflick to Walford: the role of T cell replicative senescence in human aging
Effros, R. B. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.03.004 · Cited by 61 · see citing works
Self-citationNg, 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 · see citing works
Kleemeier Award Lecture 2008 – the canary in the coal mine: telomeres and human healthspan
Effros, R. B. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp001 · Cited by 58 · see citing works
CTLA-4 upregulation during aging
Leng, Q., Bentwich, Z., & Borkow, G. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00077-5 · Cited by 57 · see citing works
Xu, J., Vallejo, A. N., Jiang, Y.-F., Weyand, C. M., & Goronzy, J. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500727200 · Cited by 56 · see citing works
Aging Augments IL-17 T-cell Alloimmune Responses
Tesar, B. M., Du, W., Shirali, A., Walker, W. E., Shen, H., & Goldstein, D. R. (2008) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2008.02458.x · Cited by 55 · see citing works
Immune Biomarkers Predictive of Respiratory Viral Infection in Elderly Nursing Home Residents
Johnstone, J., Parsons, R., Botelho, F. M., Millar, J., McNeil, S., Fülöp, T., McElhaney, J. E., Andrew, M. K., Walter, S. D., Devereaux, P. J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0108481 · Cited by 55 · see citing works
“Low naïve CD8+ T-cells, high terminally differentiated CD8+ T-cells and senescent CD8+ T-cells have been described in elderly populations [10] [11] [12] [13] [14] and have been hypothesized to predict risk of infection [9, 17] .”
BackgroundResultT‐Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Residents
Johnstone, J., Parsons, R., Botelho, F. M., Millar, J., McNeil, S., Fülöp, T., McElhaney, J. E., Andrew, M. K., Walter, S. D., Devereaux, P. J., et al. (2016) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14507 · Cited by 55 · see citing works
How Immunosenescence and Inflammaging May Contribute to Hyperinflammatory Syndrome in COVID-19
Müller, L., & Benedetto, S. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222212539 · Cited by 55 · see citing works
Miles, D. J. C., Sanneh, M., Holder, B. S., Crozier, S., Nyamweya, S., Touray, E. S., Palmero, M. S., Zaman, S. M. A., Rowland‐Jones, S., van der Sande, M. A. B., et al. (2008) · Immunology · doi:10.1111/j.1365-2567.2007.02787.x · Cited by 53 · see citing works
Aging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55 · see citing works
Modern Concepts in Cardiovascular Disease: Inflamm-Aging
Puspitasari, Y. M., Ministrini, S., Schwarz, L., Karch, C., Liberale, L., & Camici, G. G. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.882211 · Cited by 54 · see citing works
“, 2009), and this could be due to the deficient expression of CD28 co-stimulatory molecule on T cells (Boucher et al., 1998) (Weiskopf et al.”
BackgroundSYSTEMIC LUPUS ERYTHEMATOSUS IN THE ELDERLY
Kammer, G. M., & Mishra, N. (2000) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70152-6 · Cited by 51 · see citing works
Monocyte and T-Cell Responses to Exercise Training in Elderly Subjects
Shimizu, K., Suzuki, N. T., Imai, T., Aizawa, K., Nanba, H., Hanaoka, Y., Kuno, S., Mesaki, N., Kono, I., & Akama, T. (2011) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e3181fc5e67 · Cited by 51 · see citing works
“decline is shown predominantly in the CD8 cells (8).”
BackgroundSharma, R., Sharma, A., Kumari, A., Kulurkar, P. M., Raj, R., Gulati, A., & Padwad, Y. S. (2017) · Biogerontology · doi:10.1007/s10522-017-9696-6 · Cited by 51 · see citing works
“The costimulatory molecule CD28 plays a critical role in stimulation of T cells in response to pathogens and shows a characteristic decrease with age (Weng et al. 2009; Boucher et al. 1998).”
BackgroundEffros, R. B. (2004) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-004-0508-x · Cited by 48 · see citing works
“The premature cessation of telomerase induction in the CD8 versus CD4 subset seen under the controlled conditions of cell culture may explain the in vivo preponderance of CD8 T cells versus CD4 T cells with characteristics suggestive of senescence during aging [8] and chronic infection [31].”
BackgroundSelf-citationEffects of Ageing on the Immunoregulation of Parasitic Infection
Humphreys, N. E., & Grencis, R. K. (2002) · Infection and Immunity · doi:10.1128/iai.70.9.5148-5157.2002 · Cited by 48 · see citing works
“Here we investigate whether lymphocytes from our colony of ageing C57BL/Icrfa mice show a similar phenotype to that seen in other ageing mice (9).”
BackgroundInfluentialKennedy, R. B., Ovsyannikova, I. G., Haralambieva, I. H., Oberg, A. L., Zimmermann, M. T., Grill, D. E., & Poland, G. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00450 · Cited by 45 · see citing works
“It has been proposed that CD28 downregulation occurs in response to chronic immune stimulation in older individuals (72).”
BackgroundLong-term immunological memory against viruses
Effros, R. B. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00207-4 · Cited by 45 · see citing works
Self-citationBen‐Smith, A., Gorak‐Stolinska, P., Floyd, S., Weir, R. E., Lalor, M. K., Mvula, H., Crampin, A. C., Wallace, D. L., Beverley, P. C. L., Fine, P., et al. (2008) · BMC Infectious Diseases · doi:10.1186/1471-2334-8-139 · Cited by 43 · see citing works
“This is the first study to show such a difference in proportions of naïve T cells in age-matched adolescents from two countries although this has been described for elderly (>60 year olds) compared to younger individuals [24,29].”
ResultTraitanon, O., Gorbachev, A. V., Bechtel, J., Keslar, K. S., Baldwin, W. M., Poggio, E. D., & Fairchild, R. L. (2014) · American Journal of Transplantation · doi:10.1111/ajt.12719 · Cited by 41 · see citing works
“Accumulation of CD28 memory CD8þ T cells is a prominent feature of age-associated changes in T cell function (12,13).”
BackgroundHuman CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype
Narsale, A. A., Moya, R., & Davies, J. D. (2018) · Clinical Immunology · doi:10.1016/j.clim.2018.01.003 · Cited by 41 · see citing works
“CD25+CD127hi cells are a mix of central memory and effector memory cells CD25+CD127hi cells makeup around 20% of total CD4+ memory T cells and are evident both within the CM (CD197+ CD28+) and EM (CD197−) compartments of the CD45RO+ memory cell compartment.”
BackgroundInfluentialGardner, J. K., Mamotte, C. D. S., Jackaman, C., & Nelson, D. J. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.07.002 · Cited by 40 · see citing works
“In contrast, CD28 expression on human CD8+ and CD4+ T cells declines during aging (Boucher et al., 1998; Effros et al., 1994; Fagnoni et al., 1996; Leng et al., 2002; Vallejo et al., 1998; Warrington et al., 2003; Weng et al., 2009; Weyand et al., 1998), and this is paralleled by increased CTLA-4 expression on elderly…”
Gamberg, J., Pardoe, I. U., Bowmer, M. I., Howley, C., & Grant, M. D. (2004) · Immunology and Cell Biology · doi:10.1111/j.1440-1711.2004.01204.x · Cited by 38 · see citing works
Bonanno, M., Papa, D., Cerasa, A., Maggio, M. G., & Calabrò, R. S. (2024) · Medicina · doi:10.3390/medicina60020285 · Cited by 40 · see citing works
“While healthy individuals may exhibit flexibility in responding to stress, aging and diseases compromise this adaptability, potentially leading to stress-related immune dysregulation with clinical implications [48,49].”
BackgroundMulti-color flow cytometry for evaluating age-related changes in memory lymphocyte subsets in dogs
Withers, S. S., Moore, P. F., Chang, H., Choi, J. W., McSorley, S. J., Kent, M. S., Monjazeb, A. M., Canter, R. J., Murphy, W. J., Sparger, E. E., et al. (2018) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2018.05.022 · Cited by 37 · see citing works
“Interestingly, the association of aging with an increase in circulating CD28- T cells, particularly from the CD8+ lineage, is well documented in both primates and humans (Boucher et al., 1998; Dennett et al., 2002; Weng et al., 2009).”
Dolcetti, R., & Rossi, A. D. (2010) · Medicinal Research Reviews · doi:10.1002/med.20211 · Cited by 33 · see citing works
“Moreover, crosssectional analysis of T cells from different age groups clearly showed that the number of CD28 T cells progressively increased with age.(54) Consistently, ex vivo analyses demonstrated that telomeres of CD28 T cells were shorter than those of other T lymphocytes from the same individuals, suggesting a m…”
BackgroundAging, imbalanced inflammation and viral infection
Goldstein, D. R. (2010) · Virulence · doi:10.4161/viru.1.4.12009 · Cited by 35 · see citing works
Immunophenotyping and T-cell proliferative capacity in a healthy aged population
Peres, A., Bauer, M. E., da Cruz, I. B. M., Nardi, N. B., & Chies, J. A. B. (2003) · Biogerontology · doi:10.1023/a:1026282917406 · Cited by 35 · see citing works
“has been shown to be reduced in aged subjects (Effros 1997; Boucher et al. 1998; Pawelec et al. 1999).”
BackgroundHabitual exercise did not affect the balance of type 1 and type 2 cytokines in elderly people
Ogawa, K., Oka, J., Yamakawa, J., & Higuchi, M. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00167-2 · Cited by 34 · see citing works
Psychoneuroimmunology examined: The role of subjective stress.
Thornton, L. M., & Andersen, B. L. (2006) · PubMed · Cited by 34 · see citing works
Witkowski, J. M., & Bryl, E. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.10.028 · Cited by 34 · see citing works
Frailty impacts immune responses to Moderna COVID-19 mRNA vaccine in older adults
Semelka, C., DeWitt, M., Blevins, M. W., Holbrook, B. C., Sanders, J. W., & Alexander‐Miller, M. A. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00327-x · Cited by 33 · see citing works
“age and impaired vaccine responses from the established immune aging literature [43, 45, 46, 80].”
BackgroundMethodEffros, R. B. (2000) · Microbes and Infection · doi:10.1016/s1286-4579(00)00283-5 · Cited by 32 · see citing works
Self-citationLiu, W., Zhu, P., Li, M., Li, Z., Yu, Y., Liu, G., Du, J., Wang, X., Yang, J., Tian, R., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112740 · Cited by 29 · see citing works
Revisiting T-cell adhesion molecules as potential targets for cancer immunotherapy: CD226 and CD2
Jo, Y., Sim, H.-I., Yun, B., Park, Y., & Jin, H. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01317-9 · Cited by 31 · see citing works
Martínez-Taboada, V. M., Bartolomé, M. J., Amado, J., Blanco, R., García‐Unzueta, M. T., Rodrı́guez-Valverde, V., & López‐Hoyos, M. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00116-1 · Cited by 29 · see citing works
Problems and solutions to the development of vaccines in the elderly
Effros, R. B. (2003) · Immunology and Allergy Clinics of North America · doi:10.1016/s0889-8561(02)00055-3 · Cited by 27 · see citing works
“The CD28 molecule is expressed on more than 99% of human T cells at birth, but the proportion of T cells that are CD28 progressively increases with age, particularly within the CD8 T-cell subset [58], which is the major immune mediator of viral clearance.”
BackgroundSelf-citationLeng, J., Stout-Delgado, H. W., Kavita, U., Jacobs, A., Tang, J. T., Du, W., Tussey, L., & Goldstein, D. R. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.08.027 · Cited by 26 · see citing works
“Aging also impairs T-cell CD28 surface upregulation [10] and immune synapse formation [11].”
BackgroundKatz, 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
“Human CD28 expression is ubiquitous at birth, and declines with age (Boucher et al., 1998; Effros, 2000).”
Background
- Authors
- Boucher, N., Dufeu-Duchesne, T., Vicaut, E., Farge, D., Effros, R. B., & Schächter, F.
- Affiliations
- Fondation Jean Dausset-CEPH (FR)
- Hôpital Saint-Louis (FR)
- University of California, Los Angeles (US)
- Corresponding author
- Schächter, François
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 33
- Issue
- 3
- Pages
- 267-282
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1973076242
- Semantic Scholar
- 56c903c155c96dbf324ec10a879404754b4df8af
- Cited by
- 194
- References
- 65
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 3 · 2012: 5
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- CD28, T cell senescence, centenarians, human longevity, CD8+ T cells, immunosenescence, T cell responsiveness, mitogen stimulation, chronic immune stimulation, CD4+ T cells
- MeSH terms
- Adult, Aged, Aged, 80 and over, Blood Cells, Cell Division, Cells, Cultured, Humans, Longevity, T-Lymphocytes, Cellular Senescence, CD28 Antigens
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