Age-related differences in polyfunctional T cell responses

Van Epps, Puja; Banks, Richard; Aung, Htin; Betts, Michael R; Canaday, David H

doi:10.1186/1742-4933-11-14

Cited by 24T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesPsoriasis: Treatment and Pathogenesis

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

Age-related differences in polyfunctional T cell responses

Open access

Van Epps, Puja, Banks, Richard, Aung, Htin, Betts, Michael R, Canaday, David H·2014·Immunity & Ageing

DOI 10.1186/1742-4933-11-14PMC PMC4265991

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: A reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. In this study we compared the individual and polyfunctional expression of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 by T cell subsets, including the newly described stem cell like memory T cells (TSCM), in response to stimulation with superantigen staphylococcal enterotoxin B (SEB) in older (median age 80, n = 23) versus younger (median age 27; n = 23) adults. RESULTS: Older age was associated with a markedly lower frequency of CD8+ naïve T cells (11% vs. 47%; p < 0.0001) and an expansion in memory T cell subsets including central memory (p < 0.05), effector memory and effector T cells (p < 0.001 for both). There was also a decline in CD4+ naïve T cells in older subjects (33% vs. 45%; p = 0.02). There were no differences in frequencies or polyfunctional profiles of TSCM between groups. CD8+ naïve cells in the older group had increased expression of all functional parameters measured compared to the younger subjects and exhibited greater polyfunctionality (p = 0.04). CD4+ naïve T cells in the older group also showed greater polyfunctionality with a TNF-α and IL-2 predominance (p = 0.005). CD8+ effector memory and effector T cells exhibited increased polyfunctionality in the older group compared with younger (p = 0.01 and p = 0.003). CONCLUSIONS: These data suggest that aging does not have a negative effect on polyfunctionality and therefore this is likely not a major contributor to the immunesenescence described with aging.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1186/1742-4933-11-14

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

There is no difference in the frequency of TSCM between young and old groups.
“A study showed that there was no difference in the frequency of TSCM between the young and old groups [105].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [105]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells
Betts, M. R. (2006) · Blood · doi:10.1182/blood-2005-12-4818 · Cited by 1,812
Self-citation
Cytotoxic T-Cell Immunity to Influenza
McMichael, A. J., Gotch, F. M., Noble, G. R., & Beare, P. A. (1983) · New England Journal of Medicine · doi:10.1056/nejm198307073090103 · Cited by 931
The aging of the immune system
Weiskopf, D., Weinberger, B., & Grubeck-Loebenstein, B. (2009) · Transplant International · doi:10.1111/j.1432-2277.2009.00927.x · Cited by 908
Immunosenescence of ageing
Gruver, A., Hudson, L., & Sempowski, G. (2007) · The Journal of Pathology · doi:10.1002/path.2104 · Cited by 834
Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover
Almeida, J. R., Price, D. A., Papagno, L., Arkoub, Z. A., Sauce, D., Bornstein, E. R., Asher, T. E., Samri, A., Schnuriger, A., Theodorou, I. D., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070784 · Cited by 725
Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people
Koch, S. D., Larbi, A., Derhovanessian, E., Özcelik, D., Naumova, E. J., & Pawelec, G. (2008) · Immunity & Ageing · doi:10.1186/1742-4933-5-6 · Cited by 360
Human T Cell Aging and the Impact of Persistent Viral Infections
Fülöp, T., Larbi, A., & Pawelec, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00271 · Cited by 347
Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination—an impact of immunosenescence
Trzonkowski, P., Myśliwska, J. M., Szmit, E., Wickiewicz, J., Łukaszuk, K., Brydak, L. B., Machała, M. K., & Myśliwski, A. (2003) · Vaccine · doi:10.1016/s0264-410x(03)00309-8 · Cited by 341
VZV T Cell-Mediated Immunity
Weinberg, A., & Levin, M. J. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_31 · Cited by 232
When aging reaches CD4+ T-cells: phenotypic and functional changes
Moro‐García, M. A. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00107 · Cited by 216
Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells
Lugli, E., Gattinoni, L., Roberto, A., Mavilio, D., Price, D. A., Restifo, N. P., & Roederer, M. (2012) · Nature Protocols · doi:10.1038/nprot.2012.143 · Cited by 209
Immunosenenescence: role of cytomegalovirus
Pawelec, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.010 · Cited by 163
Adults 65 Years Old and Older Have Reduced Numbers of Functional Memory T Cells to Respiratory Syncytial Virus Fusion Protein
Cherukuri, A., Patton, K., Gasser, R. A., Zuo, F., Woo, J. C., Esser, M. T., & Tang, R. S. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00580-12 · Cited by 120
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 98
CMV Latent Infection Improves CD8+ T Response to SEB Due to Expansion of Polyfunctional CD57+ Cells in Young Individuals
Pera, A., Campos, C., Corona, A., Sánchez-Correa, B., Tarazona, R., Larbi, A., & Solana, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088538 · Cited by 90
The impact of aging on memory T cell phenotype and function in the human bone marrow
Herndler‐Brandstetter, D., Landgraf, K., Tzankov, A., Jenewein, B., Brunauer, R., Laschober, G. T., Parson, W., Kloss, F. R., Gassner, R. J., Lepperdinger, G., et al. (2011) · Journal of Leukocyte Biology · doi:10.1189/jlb.0611299 · Cited by 89
Limited HIV Infection of Central Memory and Stem Cell Memory CD4+ T Cells Is Associated with Lack of Progression in Viremic Individuals
Klatt, N. R., Bosinger, S. E., Peck, M. C., Richert-Spuhler, L. E., Heigele, A., Gile, J., Patel, N. B., Taaffe, J. E., Jülg, B. D., Camerini, D., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004345 · Cited by 89
The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
Lelic, A., Verschoor, C. P., Ventresca, M., Parsons, R., Evelegh, C. M., Bowdish, D. M. E., Betts, M. R., Loeb, M. B., & Bramson, J. L. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003076 · Cited by 86
Self-citation
Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns
Thomas, D. Y., Dauwalder, O., Brun, V., Badiou, C., Ferry, T., Étienne, J., Vandenesch, F., & Lina, G. (2009) · Infection and Immunity · doi:10.1128/iai.01388-08 · Cited by 85
Clinical and immunologic predictors of influenza illness among vaccinated older adults
Shahid, Z., Kleppinger, A., Gentleman, B., Falsey, A. R., & McElhaney, J. E. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.07.036 · Cited by 75
Aging and impaired immunity to influenza viruses: Implications for vaccine development
Liu, W. M., van der Zeijst, B. A. M., Boog, C. J. P., & Soethout, E. C. (2011) · Human Vaccines · doi:10.4161/hv.7.0.14568 · Cited by 61
Age is an important determinant in humoral and T cell responses to immunization with hepatitis B surface antigen
Rosenberg, C. A., Bovin, N. V., Bram, L. V., Flyvbjerg, E., Erlandsen, M., Vorup‐Jensen, T., & Petersen, E. (2013) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.24480 · Cited by 52
Immune Senescence and Vaccination in the Elderly
Lang, P., Govind, S., ten Bokum, A. M. C., Kenny, N., Matas, E., Pitts, D., & Aspinall, R. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660181 · Cited by 33
Systemic varicella zoster virus reactive effector memory T‐cells impaired in the elderly and in kidney transplant recipients
van Besouw, N. M., Verjans, G. M. G. M., Zuijderwijk, J. M., Litjens, N. H. R., Osterhaus, A. D. M. E., & Weimar, W. W. (2012) · Journal of Medical Virology · doi:10.1002/jmv.23427 · Cited by 31
Cycling Memory CD4+T Cells in HIV Disease Have a Diverse T Cell Receptor Repertoire and a Phenotype Consistent with Bystander Activation
Jiang, W., Younes, S., Funderburg, N., Mudd, J. C., Espinosa, E., Davenport, M. P., Babineau, D. C., Sieg, S. F., & Lederman, M. M. (2014) · Journal of Virology · doi:10.1128/jvi.00017-14 · Cited by 30
T Cell Activation but Not Polyfunctionality after Primary HIV Infection Predicts Control of Viral Load and Length of the Time without Therapy
Cossarizza, A., Bertoncelli, L., Nemes, E., Lugli, E., Pinti, M., Nasi, M., Biasi, S. D., Gibellini, L., Montagna, J. P., Vecchia, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050728 · Cited by 28
Intrinsic defects in CD8 T cells with aging contribute to impaired primary antiviral responses
Jiang, J. K., Fisher, E. M., & Murasko, D. M. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.02.027 · Cited by 25

Flagged first, then by citations

Sorted by citations

Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510
Influence of immune aging on vaccine responses
Gustafson, C. E., Kim, C., Weyand, C. M., & Goronzy, J. J. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.03.017 · Cited by 292
Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection
Tu, W., & Rao, S. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02111 · Cited by 192
Influence of Aging and Environment on Presentation of Infection in Older Adults
Chakhtoura, N. G. E., Bonomo, R. A., & Jump, R. (2017) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2017.07.017 · Cited by 126
Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating CD8+ Memory Stem Cells in Acquired Aplastic Anemia
Hosokawa, K. T., Muranski, P. J., Feng, X., Townsley, D. M., Liu, B., Knickelbein, J. E., Keyvanfar, K., Dumitriu, B., Ito, S., Kajigaya, S., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501739 · Cited by 102
Immunosenescence: the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis
Grebenciucova, E., & Berger, J. R. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0771-9 · Cited by 75
Parameters of the Immune System and Vitamin D Levels in Old Individuals
Alves, A. S., Ishimura, M. E., Duarte, Y. A. D. O., & Bueno, V. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01122 · Cited by 49
Defects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency
Kim, C., Jadhav, R. R., Gustafson, C. E., Smithey, M. J., Hirsch, A. J., Uhrlaub, J. L., Hildebrand, W. H., Nikolich‐Žugich, J., Weyand, C. M., & Goronzy, J. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.044 · Cited by 47
Differences Between Pediatric and Adult T Cell Responses to In Vitro Staphylococcal Enterotoxin B Stimulation
Rudolph, M. E., McArthur, M. A., Barnes, R. S., Magder, L. S., Chen, W. H., & Sztein, M. B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00498 · Cited by 39
CMV-Specific T-cell Responses at Older Ages: Broad Responses With a Large Central Memory Component May Be Key to Long-term Survival
Bajwa, M., Vita, S., Vescovini, R., Larsen, M., Sansoni, P., Terrazzini, N., Caserta, S., Thomas, D. W., Davies, K. A., Smith, H. E., et al. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix080 · Cited by 30
Vδ2+ and α/β T cells show divergent trajectories during human aging
Tan, C. T. Y., Wistuba‐Hamprecht, K., Xu, W., Nyunt, M. S. Z., Vasudev, A., Lee, B. T. K., Pawelec, G., Puan, K. J., Rötzschke, O., Ng, T. P., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.10096 · Cited by 24
Lung transplant recipients with idiopathic pulmonary fibrosis have impaired alloreactive immune responses
Wang, P., Leung, J., Lam, A., Lee, S., Calabrese, D. R., Hays, S. R., Golden, J. A., Kukreja, J., Singer, J. P., Wolters, P. J., et al. (2021) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2021.11.012 · Cited by 24
Age-Associated Heterogeneity of Ty21a-Induced T Cell Responses to HLA-E Restricted Salmonella Typhi Antigen Presentation
Rudolph, M. E., McArthur, M. A., Magder, L. S., Barnes, R. S., Chen, W. H., & Sztein, M. B. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00257 · Cited by 16
Functional Diversity of Cytomegalovirus–Specific T Cells Is Maintained in Older People and Significantly Associated With Protein Specificity and Response Size
Bajwa, M., Vita, S., Vescovini, R., Larsen, M., Sansoni, P., Terrazzini, N., Caserta, S., Thomas, D. W., Davies, K. A., Smith, H. E., et al. (2016) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw371 · Cited by 16
Anti-Inflammatory Klotho Protein Serum Concentration Correlates with Interferon Gamma Expression Related to the Cellular Activity of Both NKT-like and T Cells in the Process of Human Aging
Kaszubowska, L., Foerster, J., Kaczor, J. J., Karnia, M. J., & Kmieć, Z. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098393 · Cited by 14
T-cell aging in end-stage renal disease: an evolving story with CMV
Yang, T. O., Chuang, Y., & Chiu, Y. (2019) · Medical Microbiology and Immunology · doi:10.1007/s00430-019-00596-8 · Cited by 10
Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection
Jin, W., Fang, M., Sayın, I., Smith, C. A., Hunter, J., Richardson, B., Golden, J. B., Haley, C., Schmader, K. E., Betts, M. R., et al. (2023) · Pathogens and Immunity · doi:10.20411/pai.v7i2.560 · Cited by 8
Self-citation
Aβ‐reactive T cell polyfunctionality response as a new biomarker for mild cognitive impairment
Chiu, Y., Yan, S., Fan, Y., Chang, C., Hung, R., Liu, Y., Yang, T. O., & Chuang, Y. (2025) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.70042 · Cited by 4
Distribution and function of human long-lasting T cells in aging and non-small cell lung cancer
Tan, J. X., Yu, H. R., Gu, Y., & Hong, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1788541 · Cited by 2
Polyfunctional T peripheral helper cells are associated with the magnitude and durability of antibody responses after COVID‐19
Tungatt, K., Gomes, G. M. C., Fewings, N., Stubis, A., Doyle, C. M., Merheb, V., Aggarwal, A., Byth, K., Robertson, H., Dervish, S., et al. (2025) · Clinical & Translational Immunology · doi:10.1002/cti2.70070 · Cited by 1
The neutrophil‐to‐lymphocyte ratio as a marker of immunosenescence and COVID‐19 outcomes in the elderly: A narrative review
Gasmi, M., Torabinasab, K., Williams‐Hooker, R., Marsigliante, S., & Muscella, A. (2026) · Physiological Reports · doi:10.14814/phy2.70682 · Cited by 4
Characterisation of T cell responses to human cytomegalovirus (HCMV) in different age groups
Bajwa, M. (2016)
ANALISIS FAKTOR RISIKO USIA, JENIS KELAMIN DAN INDEKS MASSA TUBUH TERHADAP KEJADIAN KUSTA DIRUMAH SAKIT TADJUDDIN CHALID MAKASSAR TAHUN 2023
Ilyas, A. M., Abdi, D. A., Safei, I., Royani, I., & Yuniati, L. (2024) · Jurnal Kesehatan Tambusai · doi:10.31004/jkt.v5i4.36902
Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell functionPreprint
Bitsko, E. N., Joyner, D., Maslanka, J. R., Woloszczuk, K., Edgerton, A. O., Bell, M. R., Sell, C., Alameh, M., Beld, J., Haddad, E. K., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.04.730208

Polyfunctionality of naive T cells is enhanced in older age (CCR3P.223)
Eps, P. V., Banks, R. E., Aung, H. L., Betts, M. R., & Canaday, D. H. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.192.supp.115.20
Self-citation
Polyfunctional capacity of T cell function in older adults (47.10)
Canaday, D. H., Burant, C. J., Banks, R. E., Aung, H. L., Hornick, T. R., & Higgins, P. A. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.188.supp.47.10
Self-citation
Multicolor flow cytometric analysis of mouse T cell subsets in aging (159.4)
Ernst, D. N., Gao, G., O'Donnell, E. A., Elia, J., Wu, X., Chronopoulou, E., Sepulveda, H., & Hingorani, R. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.186.supp.159.4
Age-related differences in phenotype and function of CD4+ T cells are due to a phenotypic shift from naive to memory effector CD4+ T cells
Kovaiou, R. D., Weiskirchner, I., Keller, M., Pfister, G., Cioca, D., & Grubeck‐Loebenstein, B. (2005) · International Immunology · doi:10.1093/intimm/dxh314 · Cited by 76
Comparative kinetic analyses of gene profiles of naïve CD4+ and CD8+ T cells from young and old animals reveal novel age‐related alterations
Mirza, N. N., Pollock, K., Hoelzinger, D. B., Dominguez, A. L., & Lustgarten, J. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00730.x · Cited by 33

Authors: Van Epps, P., Banks, R., Aung, H., Betts, M. R., & Canaday, D. H.
Affiliations: Louis Stokes Cleveland VA Medical Center (US)
University of Pennsylvania (US)
Corresponding author: Canaday, David H
ORCID: Aung, Htin
Betts, Michael R
Canaday, David H
Venue: Immunity & Ageing
Publisher: Springer Science and Business Media LLC
Published: 2014-10-23
Volume: 11
Issue: 1
Pages: 14-14
ISSN: 1742-4933 (ISSN-L)
DOI: 10.1186/1742-4933-11-14
PMC: PMC4265991
OpenAlex: W2108412505
Cited by: 22
References: 27
Citations by year: 2026: 2 · 2025: 2 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 5
FWCI: 1.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Immunity & Ageing (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: immunosenescence, T cell polyfunctionality, T cell senescence, naive T cells, stem cell-like memory T cells, CD8+ T cells, CD4+ T cells, effector memory T cells, superantigen stimulation, staphylococcal enterotoxin B, interferon-gamma, TNF-α, interleukin-2, perforin, MIP-1α, age-related immune decline

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

Age-related differences in polyfunctional T cell responses

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks