The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Expansion of cytotoxic CD8 + CD28 − T cells in healthy ageing people, including centenarians
Abstract
Ageing is associated with complex remodelling in the phenotypic and functional profiles of T lymphocytes. We investigated whether expression of CD28 antigen on T cells is conserved throughout adulthood and ageing in humans. For this purpose we analysed T cells obtained from peripheral blood of 102 healthy people of ages ranging from 20 to 105 years. We found an age‐related increase of CD28 − T cells in percentage and absolute number, predominantly among CD8 + T cells. CD28 − T cells from aged donors analysed by flow cytometry appeared as resting cells (not expressing CD25, CD38, CD69, CD71, DR), bearing markers of cytotoxic activity (CD11b and CD57) and with a phenotype compatible with ‘memory’ cells (up‐regulated CD2 and CD11a; CD62L absent). At the functional level, freshly isolated purified CD28 − CD8 + T cells showed high anti‐CD3 redirected cytotoxic activity against Fc‐bearing P815 cells. The same activity tested on freshly isolated bulk T lymphocytes was significantly augmented with age. We found a positive correlation between age, number of CD8 + CD28 − T cells and anti‐CD3 redirected cytotoxicity by freshly isolated T cells. These data suggest that an activation of unknown nature within the cytotoxic arm of the immune system occurs with age. We speculate that these cytotoxic T lymphocytes (CTL) in vivo may constitute armed effector cells for immediate killing of targets bearing peptides from pathogens of intracellular origin.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“An established hallmark of adaptive immune ageing is the expansion of the memory population of highly cytotoxic CD8+CD28− T cells114”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [114]
Citations
Cites
Human Aging: Usual and Successful
Rowe, J. W., & Kahn, R. L. (1987) · Science · doi:10.1126/science.3299702 · Cited by 3,384
Schwartz, R. H. (1992) · Cell · doi:10.1016/s0092-8674(05)80055-8 · Cited by 1,293
Linsley, P. S., Brady, W., Grosmaire, L. S., Aruffo, A. A., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.721 · Cited by 1,126
Sanders, M. E., Makgoba, M. W., Sharrow, S. O., Stephany, D., Springer, T. A., Young, H. A., & Shaw, S. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.5.1401 · Cited by 906
Signals and signs for lymphocyte responses
Janeway, C. A., & Bottomly, K. (1994) · Cell · doi:10.1016/0092-8674(94)90335-2 · Cited by 849
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
Role of the CD28 receptor in T-cell activation
June, C. H., Ledbetter, J. A., Linsley, P. S., & Thompson, C. B. (1990) · Immunology Today · doi:10.1016/0167-5699(90)90085-n · Cited by 674
The immunology of exceptional individuals: the lesson of centenarians
Franceschi, C., Monti, D., Sansoni, P., & Cossarizza, A. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80064-6 · Cited by 535
Self-citationCD8 naive T cell counts decrease progressively in HIV-infected adults.
Roederer, M., Dubs, J. G., Anderson, M. T., Raju, P. A., Herzenberg, L. A., & Herzenberg, L. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117892 · Cited by 489
Sansoni, P., Cossarizza, A., Brianti, V., Fagnoni, F. F., Snelli, G., Monti, D., Marcato, A., Passeri, G., Ortolani, C., & Forti, E. (1993) · Blood · doi:10.1182/blood.v82.9.2767.2767 · Cited by 457
Self-citation
Cited by
Sorted by citations
Items 301–363 of 363
Innate Immune System Modulation During Aging: Contributions of Macrophages and Dendritic Cells
Maletto, B. A., Morón, G., & Pistoresi-Palencia, M. C. (2010) · Current Immunology Reviews · doi:10.2174/1573395511006040329 · Cited by 3
Herr, F., Brunel, M., Roders, N., & Dürrbach, A. (2016) · Drugs · doi:10.1007/s40265-016-0656-2 · 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
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
Altered Expression of Costimulatory Molecules in Patients With Polymyositis
Takamure, M., Murata, K., Sugie, K., & Ueno, S. (2005) · Journal of Clinical Neuromuscular Disease · doi:10.1097/01.cnd.0000161529.91988.0b · Cited by 2
Thude, H., Kramer, K., Koch, M., Peine, S., Sterneck, M. R., & Nashan, B. (2014) · Human Immunology · doi:10.1016/j.humimm.2014.09.024 · Cited by 2
CMV Infection and Frailty: Immunologic Consequences and Disease Pathogenesis
Wang, G. C., Chiu, Y., & Walston, J. D. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_63 · Cited by 2
Solana, R., & Pawelec, G. (2004) · Neuroimmune biology · doi:10.1016/s1567-7443(04)80003-6 · Cited by 3
Altersspezifische Veränderungen des Immunsystems und deren assoziierte Krankheitsbilder
Rink, L., & Dalhoff, K. (2004) · Springer eBooks · doi:10.1007/978-3-642-18741-4_16 · Cited by 2
Interactions Between Advanced Age and HIV Cognitive Impairment
Valcour, V., & McMurtray, A. M. (2009) · Humana Press eBooks · doi:10.1007/978-1-59745-434-6_18 · Cited by 2
MHC-Unrestricted Cytotoxicity in Ageing
Provinciali, M., Donnini, A., & Re, F. (2004) · Neuroimmune biology · doi:10.1016/s1567-7443(04)80007-3 · Cited by 2
Vavřinec, J., Hromadníková, I., Štechová, K., Vavrincova, P., Hridelova, D., Nekvasilova, H., & Reitzova, H. (2002) · Arthritis Research · doi:10.1186/ar516 · Cited by 2
Casado, J. G., DelaRosa, O., Peralbo, E., Tarazona, R., & Solana, R. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)13007-0 · Cited by 2
Finamore, A., Roselli, M., & Mengheri, E. (2009) · Food Science & Technology Bulletin Functional Foods · doi:10.1616/1476-2137.15773 · Cited by 1
Thymic Regeneration in Mice and Humans Following Sex Steroid Ablation
Fletcher, A. L., Reiseger, J. J., Vlahos, K., Seach, N., Dudakov, J. A., Chidgey, A. P., & Boyd, R. L. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_74 · Cited by 1
Toxic Memories in Systemic Sclerosis
Duffy, L., & O’Reilly, S. (2017) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2017.02.968 · Cited by 1
Role of Cytomegalovirus in Driving Cytotoxic CD28null T Cells
Pera, A., Bano, A., & Kern, F. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_124 · Cited by 1
Hashimoto, H., Sterk, M., & Schilbach, K. (2017) · Immunologic Research · doi:10.1007/s12026-017-8976-1 · Cited by 1
Stojić-Vukanić, Z., Pilipović, I., Arsenović-Ranin, N., Dimitrijević, M., & Leposavić, G. (2021) · Immunology Letters · doi:10.1016/j.imlet.2021.08.003 · Cited by 1
Age- and Race-Related Changes in Subpopulations of Peripheral Blood Lymphocytes in Humans
Hooten, N. N., Longo, D. L., & Evans, M. K. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_85 · Cited by 1
Generation and Gene Expression of CD28-CD8 T-cells in Human
Weng, N. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_17 · Cited by 1
Pathological Relevance of the Natural Immune System
Salvioli, S., Capri, M., Fumelli, C., Lescai, F., Franceschi, C., & Monti, D. (2005) · Neuroimmune biology · doi:10.1016/s1567-7443(05)80021-3 · Cited by 1
Self-citationHuman Cytomegalovirus as a driving force towards Immunosenescence
Zadražil, Z. (2018) · doi:10.32657/10356/73417 · Cited by 1
Alterations in signal transduction inT lymphocytes and neutrophils with ageing
Fülöp, T., Hirokawa, K., Dupuis, G., Larbi, A., & Pawelec, G. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)13006-9 · Cited by 1
Larbi, A., & Fülöp, T. (2004) · Neuroimmune biology · doi:10.1016/s1567-7443(04)80006-1
T cell ageing and immune surveillance
McLeod, J. (2002) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(02)13009-4
Regulation and role of IL-7 production in HIV-1 infection
Thắng, P. H. (2011) · Figshare
Introduction: Knowledge is survival—The mission of the immune system and its stochastic simulations
Celada, F. (2011) · Autoimmunity · doi:10.3109/08916934.2010.523239
T CELL SUBSETS AND DISEASE MECHANISMS IN INFLAMMATORY MYOPATHIES
Pandya, J. M. (2014) · Figshare
Análise de parâmetros psiconeuroimunológicos em longevos saudáveis
de Oliveira, Á. S. (2014)
Griffiths, S. (2011) · UCL Discovery (University College London)
Immunity, Inflammation and infections during aging
Capri, M., Salvioli, S., Sevini, F., Cevenini, E., Pierini, M., Celani, L., Bucci, L., Ostan, R., Scurti, M., Mazzà, D., et al. (2007) · Springer eBooks · doi:10.1007/1-4020-5058-5_2
Self-citationEffects of Moderate Exercise on Age-associated Changes of Immune Functions in Mammal
Kim, H., Cho, Y. M., Ko, Y., & Seong, H. (2015) · Journal of Agriculture & Life Science · doi:10.14397/jals.2014.49.1.115
Modelli Stocastici del Sistema Immunitario: Risposta Adattativa, Memoria e Longevita
Mariani, L., & Turchetti, G. (2001)
Human Longevity Aging of the Immune System as a Prognostic Factor for
Larbi, A., Franceschi, C., Mazzatti, D. J., Solana, R., & Wikby, A. (2016)
Self-citationWoods, J. A., Pence, B. D., Martin, S., & Cook, M. D. (2013) · CRC Press eBooks · doi:10.1201/b13781-61
Cellular Aging and Tumor Regulation
Simm, A., Seliger, B., & Klotz, L. (2016) · Healthy ageing and longevity · doi:10.1007/978-3-319-26239-0_11
Mitochondria, Aging, and Disease
Salvioli, S., Bonafè, M., Barbi, C., Capri, M., Monti, D., & Franceschi, C. (2003) · Oxidative stress and disease · doi:10.1201/9780203912874.ch7
Self-citationO’Connor, J., Herrera, G., Jávega, B., & Martínez‐Romero, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00058-0
The Role of the Bone Marrow for Adaptive Immunity in Old Age
Grubeck‐Loebenstein, B., & Pangrazzi, L. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_170
Role of Cytomegalovirus in Driving Cytotoxic CD28null T Cells
Pera, A., Bano, A., & Kern, F. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_124-1
Engraftment and tolerance induction in cellular therapy : focus on mesenchymal stromal cells
Ljung, K. (2018) · Figshare
Chronic stress and ageing : effects on immune function
Vitlić, A. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Characteristics of the Immunoresponse in Elderly People and Autoimmunity
Moskalets, O. V. (2020) · Advances in Gerontology · doi:10.1134/s2079057020040153
Generation and Gene Expression of CD28−CD8 T Cells in Human
Kim, J., & Weng, N. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_17
Bucci, L., Ostan, R., Capri, M., Salvioli, S., Cevenini, E., Celani, L., Monti, D., & Franceschi, C. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_45
Self-citationGeneration and Gene Expression of CD28−CD8 T Cells in Human
Kim, J., & Weng, N. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_17-1
Saedi, A. A., Kirk, B., Iuliano, S., Zanker, J., Vogrin, S., Jayaram, L., Thomas, S. A., Golding, C., Navarro-Perez, D., Marušić, P., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-059075
CMV Infection and Frailty: Immunologic Consequences and Disease Pathogenesis
Wang, G. C., Chiu, Y., & Walston, J. D. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_63-1
The Role of the Bone Marrow for Adaptive Immunity in Old Age
Grubeck‐Loebenstein, B., & Pangrazzi, L. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_170-1
Immune Response and Infections in the Elderly
Bryan, N. B., & Sarwari, A. R. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316676325.011
Kondapaka, M., & Kheirbek, R. (2023) · International perspectives on aging · doi:10.1007/978-3-031-30915-1_15
Nicotinamide Adenine Dinucleotide and Immunoregulation
Mou, Y.-J., & Qin, Z.-H. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_18
Lenalidomide targets the T-cell co-stimulatory pathway to mediate immune modulation
McDaniel, J. M. (2012) · Digital Commons - University of South Florida (University of South Florida)
CD28 : nouvelles données sur un récepteur majeur de la costimulation lymphocytaire T
Morin, S. O. (2017) · theses.fr (ABES) · doi:10.70675/cb01635fz2f63z43e2zad0cz210485c4c5cf
Soongsathitanon, J., Homjan, T., Assantachai, P., Muangpaisan, W., Sae‐Lee, C., Boonnak, K., & Dharakul, T. (2026) · BMC Geriatrics · doi:10.1186/s12877-026-07456-0
Mechanisms and intervention strategies for thymic involution and T cell senescence
Liu, Y., QIAO1, X.-N., Zhang, H., & Hong-Bo, H. U. (2026) · Shengming kexue · doi:10.3724/cbls.2026101
Arnold, C. R., Mangesius, J., Weinberger, B., Portnaia, I., Santacroce, A., Ganswindt, U., & Muacevic, A. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1888282
Peripheral T-cell co-signalling states mark vulnerability and resilience to cerebral Aβ pathologyPreprint
Mallone, A., Bachmann, D., Rickenbach, C., Krueger, M., Kirabali, T., Zetterberg, H., Ferretti, M. T., Kulic, L., Höck, C., Nitsch, R. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.03.742616
Mapping Immune Responses to CMV in Renal Transplantation
Hoffman, A., Elaine, R., Sarwal, M., Elashoff, D., Bunnapradist, S. (., & Vincenti, F. (2022) · ImmPort · doi:10.21430/m30v1nqbf0
Synergistic effects of physical and psychological distress on immunesenescence
Duggal, N. A. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Metadata
- Authors
- FAGNONI, F. F., VESCOVINI, R., MAZZOLA, M., BOLOGNA, G., NIGRO, E., LAVAGETTO, G., FRANCESCHI, C., PASSERI, M., & SANSONI, P.
- Affiliations
- University of Parma (IT)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- SANSONI, P.
- ORCID
- FRANCESCHI, C.
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 1996-08
- Volume
- 88
- Issue
- 4
- Pages
- 501-507
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- OpenAlex
- W2030414136
- Cited by
- 362
- References
- 36
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 13 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 14 · 2019: 13 · 2018: 15 · 2017: 23 · 2016: 12 · 2015: 8 · 2014: 13 · 2013: 9 · 2012: 5
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD28-negative T cells, CD8+ T cells, cytotoxic T lymphocytes, aging, centenarians, T cell activation, cytotoxicity, T cell memory phenotype, CD11b, CD57, age-related immune changes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cell Separation, Cytotoxicity, Immunologic, Flow Cytometry, Humans, Middle Aged, CD3 Complex, CD28 Antigens, CD8-Positive T-Lymphocytes, Lymphocyte Count
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