Age-associated changes within CD4+ T cells

Kovaiou, Rania D.; Grubeck-Loebenstein, Beatrix

doi:10.1016/j.imlet.2006.07.006

Cited by 90T-cell and B-cell ImmunologyHIV Research and TreatmentGenetics, Aging, and Longevity in Model Organisms

Age-associated changes within CD4+ T cells

Kovaiou, Rania D., Grubeck-Loebenstein, Beatrix·2006·Immunology Letters

DOI 10.1016/j.imlet.2006.07.006

Open this paper in CoChat — free account

Abstract

As individuals age their ability to respond and clear pathogens declines, leading to a greater incidence and severity of infectious diseases. Additionally, the efficacy of vaccines is frequently decreased in elderly persons. Increased susceptibility to infections and reduced protection after vaccination reflect the impact of age-related changes on the immune system. The immune system undergoes a wide range of changes with increasing age. The aim of this review is to summarize cellular and molecular aspects of aging CD4(+) T cells. CD4(+) T cells play an essential role in mediating both humoral and cellular immune responses. Therefore, age-associated dysfunctions within CD4(+) T cells have a strong clinical impact. Improving our understanding of the aged CD4(+) T cells, in particular but also of the aged immune system in general, is crucial for developing effective prevention and treatment programs which will facilitate healthy aging and improve the quality of life of the elderly population.

Integrity signals

Registry

Crossref · 10.1016/j.imlet.2006.07.006

Cites

81 of 81 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?

The ratio of CD4+ to CD8+ lymphocytes in the BAL fluid has been shown to increase with age, suggesting a decrease in the number of naïve T cells available that can be converted to memory cells against a novel antigen.
“Specifically, the ratio of CD4+ to CD8+ lymphocytes in the BAL fluid has been shown to increase with age, suggesting a decrease in the number of naïve T cells available that can be converted to memory cells against a novel antigen (131, 132).”
From Aging and Lung Disease (2020) · cites this paper as [132]
Decreased CD4+ and CD8+ T cell responses in the elderly can impair immunity to influenza vaccination and cytotoxicity against the influenza virus, respectively.
“Decreased CD4+ and CD8+ T cell responses in the elderly can impair immunity to influenza vaccination and cytotoxicity against the influenza virus, respectively (132, 133).”
From Aging and Lung Disease (2020) · cites this paper as [132]
Memory T cell responses, T cell receptor repertoire diversity, T helper cell differentiation, and T helper cell activity diminish with age.
“Further, memory T cell responses, T cell receptor repertoire diversity, T helper cell differentiation, and T helper cell activity diminish with age (131, 132).”
From Aging and Lung Disease (2020) · cites this paper as [132]
An age-dependent increase in cytotoxic CD8+ and memory CD4+ T cells in the airways of COPD patients may further disease progression.
“An age-dependent increase in cytotoxic CD8+ and memory CD4+ T cells in the airways of COPD patients may further disease progression (86, 130, 132).”
From Aging and Lung Disease (2020) · cites this paper as [132]

Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Effector and memory T-cell differentiation: implications for vaccine development
Kaech, S. M., Wherry, E. J., & Ahmed, R. (2002) · Nature Reviews Immunology · doi:10.1038/nri778 · Cited by 1,865 · see citing works
Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections
Appay, V., Dunbar, P. R., Callan, M. F. C., Klenerman, P., Gillespie, G. M. A., Papagno, L., Ogg, G. S., King, A., Lechner, F., Spina, C. A., et al. (2002) · Nature Medicine · doi:10.1038/nm0402-379 · Cited by 1,556 · see citing works
Defective CD8 T Cell Memory Following Acute Infection Without CD4 T Cell Help
Sun, J. C., & Bevan, M. J. (2003) · Science · doi:10.1126/science.1083317 · Cited by 1,213 · see citing works
Thymus and Autoimmunity: Production of CD25+CD4+ Naturally Anergic and Suppressive T Cells as a Key Function of the Thymus in Maintaining Immunologic Self-Tolerance
Itoh, M., Takahashi, T., Sakaguchi, N., Kuniyasu, Y., Shimizu, J., Otsuka, F., & Sakaguchi, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.9.5317 · Cited by 1,209 · see citing works
Age-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,180 · see citing works
Ageing and infection
Gavazzi, G., & Krause, K.-H. (2002) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(02)00437-1 · Cited by 990 · see citing works
hnRNP complexes: composition, structure, and function
Krecic, A. M., & Swanson, M. S. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80051-9 · Cited by 813 · see citing works
The Influence of Age on T Cell Generation and TCR Diversity
Naylor, K., Li, G., Vallejo, A. N., Lee, W.-W., Koetz, K., Bryl, E., Witkowski, J., Fulbright, J., Weyand, C. M., & Goronzy, J. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.11.7446 · Cited by 802 · 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
Extrafollicular antibody responses
MacLennan, I. C. M., Toellner, K., Cunningham, A. F., Serre, K., Sze, D., Zúñiga, E. I., Cook, M., & Vinuesa, C. G. (2003) · Immunological Reviews · doi:10.1034/j.1600-065x.2003.00058.x · Cited by 642 · see citing works
A Role for CD40 Expression on CD8 + T Cells in the Generation of CD8 + T Cell Memory
Bourgeois, C., Rocha, B., & Tanchot, C. (2002) · Science · doi:10.1126/science.1072615 · Cited by 641 · see citing works
Molecular dissection of nucleolin's role in growth and cell proliferation: new insights
Srivastava, M., & Pollard, H. B. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.1911 · Cited by 495 · see citing works
CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
Schmidt, D., Goronzy, J. J., & Weyand, C. M. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118638 · Cited by 482 · see citing works
Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells
Kondrack, R. M., Harbertson, J., Tan, J. T., McBreen, M. E., Surh, C. D., & Bradley, L. M. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030735 · Cited by 470 · see citing works
Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells
Seddon, B. P., Tomlinson, P. D., & Zamoyska, R. (2003) · Nature Immunology · doi:10.1038/ni946 · Cited by 457 · see citing works
CD4+ Tregs and immune control
Fehervari, Z. T., & Sakaguchi, S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci23395 · Cited by 451 · 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 432 · 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
Perturbation of the T-cell repertoire in patients with unstable angina.
Liuzzo, G., Kopecky, S. L., Frye, R. L., Fallon, W. M. O., Maseri, A., Goronzy, J. J., & Weyand, C. M. (1999) · Circulation · doi:10.1161/01.cir.100.21.2135 · Cited by 398 · see citing works
Emergence of a CD4+CD28− Granzyme B+, Cytomegalovirus-Specific T Cell Subset after Recovery of Primary Cytomegalovirus Infection
van Leeuwen, E. M. M., Remmerswaal, E. B. M., Vossen, M. T. M., Rowshani, A. T., Dillen, P. M. E. W., van Lier, R. A. W., & ten Berge, I. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1834 · Cited by 369 · see citing works
T-cell-mediated lysis of endothelial cells in acute coronary syndromes
Nakajima, T., Schulte, S., Warrington, K. J., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2002) · Circulation · doi:10.1161/hc0502.103348 · Cited by 356 · see citing works
Aging and innate immune cells
Plackett, T. P., Boehmer, E. D., Faunce, D. E., & Kovacs, E. J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1103592 · Cited by 351 · see citing works
IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells
Li, J., Huston, G. E., & Swain, S. L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030725 · Cited by 309 · see citing works
Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion
Fletcher, J. M., Vukmanovic-Stejic, M., Dunne, P. J., Birch, K. E., Cook, J. E., Jackson, S. E., Salmon, M., Rustin, M. H., & Akbar, A. N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.12.8218 · Cited by 296 · 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
Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
Eaton, S. M., Burns, E. M., Kusser, K. L., Randall, T. D., & Haynes, L. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041395 · Cited by 279 · see citing works
Pgp‐1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A
Lerner, A., Yamada, T., & Miller, R. A. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190604 · Cited by 275 · see citing works
CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly
Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2433717100 · Cited by 270 · see citing works
Down-Regulation of CD28 Expression by TNF-α
Bryl, E., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3231 · Cited by 264 · see citing works
The role of lipid rafts in signalling and membrane trafficking in T lymphocytes
Alonso, M. A., & Millán, J. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.22.3957 · Cited by 259 · see citing works
Benign Monoclonal Gammapathy
WALDENSTRÖM, J. G. (1984) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1984.tb05032.x · Cited by 248 · see citing works
Interleukin 2, but Not Other Common γ Chain–Binding Cytokines, Can Reverse the Defect in Generation of Cd4 Effector T Cells from Naive T Cells of Aged Mice
Haynes, L., Linton, P., Eaton, S. M., Tonkonogy, S. L., & Swain, S. L. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.7.1013 · Cited by 248 · see citing works
Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection
Amyes, E., Hatton, C., Montamat‐Sicotte, D., Gudgeon, N. H., Rickinson, A. B., McMichael, A. J., & Callan, M. F. C. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20022058 · Cited by 225 · see citing works
Modulation of CD28 Expression: Distinct Regulatory Pathways During Activation and Replicative Senescence
Vallejo, A. N., Brandes, J. C., Weyand, C. M., & Goronzy, J. J. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.11.6572 · Cited by 209 · see citing works
Functional properties of CD4+CD28− T cells in the aging immune system
Weyand, C. M., Brandes, J. C., Schmidt, D., Fulbright, J. W., & Goronzy, J. J. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00161-9 · Cited by 201 · see citing works
Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine
Kang, I., Hong, M. S., Nolasco, H., Park, S. H., Dan, J. M., Choi, J.-Y., & Craft, J. E. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.1.673 · Cited by 197 · see citing works
Resistance to apoptosis and elevated expression of Bcl-2 in clonally expanded CD4+CD28− T cells from rheumatoid arthritis patients
Schirmer, M., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.2.1018 · Cited by 191 · see citing works
Aging-related Deficiency of CD28 Expression in CD4+ T Cells Is Associated with the Loss of Gene-specific Nuclear Factor Binding Activity
Vallejo, A. N., Nestel, A. R., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8119 · Cited by 179 · see citing works
Why Aging T Cells Fail: Implications for Vaccination
Haynes, L., & Swain, S. L. (2006) · Immunity · doi:10.1016/j.immuni.2006.06.003 · Cited by 169 · see citing works
Clonality and longevity of CD4+CD28null T cells are associated with defects in apoptotic pathways
Vallejo, A. N., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.11.6301 · Cited by 169 · see citing works
Immunosenescence, autoimmunity, and rheumatoid arthritis
Weyand, C. M., Fulbright, J. W., & Goronzy, J. J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00090-1 · Cited by 161 · see citing works
Early activation defects in T lymphocytes from aged mice
Miller, R. A., Gorcia, G., Kirk, C. J., & Witkowski, J. M. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01029.x · Cited by 146 · see citing works
Costimulatory molecules in Wegener's granulomatosis (WG): lack of expression of CD28 and preferential up-regulation of its ligands B7-1 (CD80) and B7-2 (CD86) on T cells
Moosig, F., Csernok, E., Wang, G., & Gross, W. L. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00695.x · Cited by 138 · see citing works
CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation
Warrington, K. J., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2003) · Blood · doi:10.1182/blood-2002-08-2574 · Cited by 132 · see citing works
Altered T cell signalling in ageing
Pawelec, G., Hirokawa, K., & Fülöp, T. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00290-1 · Cited by 131 · see citing works
Age-Dependent Alterations in the Assembly of Signal Transduction Complexes at the Site of T Cell/APC Interaction
Tamir, A., Eisenbraun, M. D., Garcia, G. G., & Miller, R. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.3.1243 · Cited by 130 · see citing works
Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging
Larbi, A., Dupuis, G., Khalil, A., Douziech, N., Fortin, C., & Fülöp, T. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.08.016 · Cited by 126 · see citing works
Phenotypic and Functional Characterization of CD4 T Cells Expressing Killer Ig-Like Receptors
van Bergen, J., Thompson, A., van der Slik, A. R., Ottenhoff, T. H. M., Gussekloo, J., & Koning, F. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.11.6719 · Cited by 124 · see citing works
Single-Cell Analyses Reveal Two Defects in Peptide-Specific Activation of Naive T Cells from Aged Mice
Garcia, G. G., & Miller, R. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.5.3151 · Cited by 123 · see citing works
Immunologic Evidence for Frequent Age-Related Cytomegalovirus Reactivation in Seropositive Immunocompetent Individuals
McVoy, M. A., & Adler, S. P. (1989) · The Journal of Infectious Diseases · doi:10.1093/infdis/160.1.1 · Cited by 120 · see citing works
Central Role of Thrombospondin-1 in the Activation and Clonal Expansion of Inflammatory T Cells
Vallejo, A. N., Muegge, L. O., Klimiuk, P. A., Weyand, C. M., & Goronzy, J. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.6.2947 · Cited by 118 · see citing works
Are regulatory T-cells linked with aging?
Dejaco, C., Duftner, C., & Schirmer, M. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.01.008 · Cited by 118 · see citing works
Naïve T Cells in the Elderly
Pfister, G., Weiskopf, D., Lazuardi, L., Kovaiou, R. D., Cioca, D., Keller, M., LORBEG, B., Parson, W., & Grubeck‐Loebenstein, B. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1354.018 · Cited by 118 · see citing works
Self-citation
The effect of age on the cognate function of CD4<sup>+</sup> T cells
Haynes, L., & Eaton, S. M. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00255.x · Cited by 116 · see citing works
Downregulation of CD28 surface antigen on CD4+ and CD8+ T lymphocytes during HIV-1 infection.
Choremi‐Papadopoulou, H., Viglis, V., Gargalianos, P., Kordossis, T., Iniotaki-Theodoraki, A. G., & Kosmidis, J. (1994) · PubMed · Cited by 107 · see citing works
Formation of the Killer Ig-Like Receptor Repertoire on CD4+CD28null T Cells
Snyder, M. R., Muegge, L., Offord, C. P., O’Fallon, W. M., Bajzer, Ž., Weyand, C. M., & Goronzy, J. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.8.3839 · Cited by 104 · see citing works
Cytokine receptor signalling and aging
Fülöp, T., Larbi, A., Douziech, N., Levesque, I., Varin, A., & Herbein, G. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.01.025 · Cited by 103 · see citing works
Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen
Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D., & Swain, S. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041933 · Cited by 102 · see citing works
Towards a cellular definition of CD8+ T-cell memory: the role of CD4+ T-cell help in CD8+ T-cell responses
Rocha, B., & Tanchot, C. (2004) · Current Opinion in Immunology · doi:10.1016/j.coi.2004.03.004 · Cited by 101 · see citing works
T-cell activation through the antigen receptor. Part 2: Role of signaling cascades in T-cell differentiation, anergy, immune senescence, and development of immunotherapy
Nel, A. E., & Slaughter, N. (2002) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2002.124965 · Cited by 96 · see citing works
Human Immunosenescence
Pawelec, G., Koch, S. D., Franceschi, C., & Wikby, A. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1354.009 · Cited by 94 · see citing works
Molecular Basis for the Loss of CD28 Expression in Senescent T Cells
Vallejo, A. N., Bryl, E., Klarskov, K., Naylor, S., Weyand, C. M., & Goronzy, J. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207352200 · Cited by 91 · see citing works
Age-Dependent Defects in TCR-Triggered Cytoskeletal Rearrangement in CD4+ T Cells
Garcia, G. G., & Miller, R. A. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.9.5021 · Cited by 90 · see citing works
HIV-1-Specific Memory CD4+ T Cells Are Phenotypically Less Mature Than Cytomegalovirus-Specific Memory CD4+ T Cells
Yue, F. Y., Kovacs, C. M., Dimayuga, R. C., Parks, P., & Ostrowski, M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.4.2476 · Cited by 88 · see citing works
Characterization of subsets of CD4 + memory T cells reveals early branched pathways of T cell differentiation in humans
Song, K., Rabin, R. L., Hill, B. J., Rosa, S. C. D., Perfetto, S. P., Zhang, H. H., Foley, J. F., Reiner, J. S., Liu, J., Mattapallil, J. J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409720102 · Cited by 87 · see citing works
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 · see citing works
Self-citation
Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific
Genova, G. D., Roddick, J., McNicholl, F. P., & Stevenson, F. K. (2005) · Blood · doi:10.1182/blood-2005-08-3255 · Cited by 73 · see citing works
Functional Disruption of the CD28 Gene Transcriptional Initiator in Senescent T Cells
Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005503200 · Cited by 71 · see citing works
Human CD4+ T Cells Are Predominantly Distributed among Six Phenotypically and Functionally Distinct Subsets
Amyes, E., McMichael, A. J., & Callan, M. F. C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.5765 · Cited by 65 · see citing works
Differential Tyrosine Phosphorylation of Zeta Chain Dimers in Mouse CD4 T Lymphocytes: Effect of Age
Garcia, G. G., & Miller, R. A. (1997) · Cellular Immunology · doi:10.1006/cimm.1996.1040 · Cited by 65 · see citing works
From 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
Maturation of CD4+ Lymphocytes in the Aged Microenvironment Results in a Memory-Enriched Population
Timm, J., & Thoman, M. L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.2.711 · Cited by 61 · see citing works
Altered Composition of the Immunological Synapse in an Anergic, Age-Dependent Memory T Cell Subset
Eisenbraun, M. D., Tamir, A., & Miller, R. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6105 · Cited by 60 · see citing works
CD8+ T‐cell clones in old mice
Ku, C., Kotzin, B. L., Kappler, J. W., & Marrack, P. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01034.x · Cited by 55 · see citing works
Age-related changes of signal transduction in T cells
Hirokawa, K. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(98)00067-9 · Cited by 49 · see citing works
What is healthy aging in the 21st century?
Westendorp, R. G. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.404s · Cited by 48 · see citing works
Tumor Necrosis Factor-α and CD80 Modulate CD28 Expression through a Similar Mechanism of T-cell Receptor-independent Inhibition of Transcription
Lewis, D. E., Merched-Sauvage, M., Goronzy, J. J., Weyand, C. M., & Vallejo, A. N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402194200 · Cited by 45 · see citing works
Age‐related defects in CD4+ T cell activation reversed by glycoprotein endopeptidase
Garcia, G. G., & Miller, R. A. (2003) · European Journal of Immunology · doi:10.1002/eji.200324310 · Cited by 35 · see citing works
Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3)
(2002) · doi:10.1002/1521-4141(200208)32:8

Flagged first, then by citations

Sorted by citations

Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
“Although Treg cells increase in number with age, their suppressing capability declines significantly, which may contribute to inflammation in the elderly.(87,88) At the molecular level, the damage to signal transduction, such as decreased CD28-mediated JNK kinase and Raf-1/MEK/ERK kinase activation, results in a hypor…”
Background
Aging and Lung Disease
Cho, S. J., & Stout-Delgado, H. W. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034610 · Cited by 458 · see citing works
Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation
Lages, C. S., Suffia, I., Velilla, P. A., Huang, B., Warshaw, G., Hildeman, D. A., Belkaid, Y., & Chougnet, C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.3.1835 · Cited by 399 · see citing works
Predictors of serological cure and serofast state after treatment in HIV-negative persons with early syphilis.
Sena, A. C., Wolff, M., Martin, D. H., Behets, F., Van Damme, K., Leone, P., Langley, C., McNeil, L., & Hook, E. W. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir671 · Cited by 132 · see citing works
Age-associated parallel increase of Foxp3+CD4+ regulatory and CD44+CD4+ memory T cells in SJL/J mice
Han, G.-M., Zhao, B., Jeyaseelan, S., & Feng, J.-M. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.05.003 · Cited by 35 · see citing works

Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review
Dinh, H. C., Beyer, I., Mets, T. F., Onyema, O. O., Njemini, R., Renmans, W., Waele, M. D., Jochmans, K., Meeren, S. V., & Bautmans, I. (2016) · Calcified Tissue International · doi:10.1007/s00223-016-0212-9 · Cited by 73 · see citing works
HIV Infection-Related Premature Immunosenescence: High Rates of Immune Exhaustion After Short Time of Infection
Ferrando‐Martínez, S., Ruíz-Mateos, E., Romero-Sánchez, M. C., Muñoz‐Fernández, M. Á., Viciana, P., Genebat, M., & Leal, M. (2011) · Current HIV Research · doi:10.2174/157016211797636008 · Cited by 37 · see citing works
Nutrition, diet and immunosenescence
Maijó, M., Clements, S. J., Ivory, K., Nicoletti, C., & Carding, S. R. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.12.003 · Cited by 85 · see citing works
Rheumatoid Arthritis: A Role for Immunosenescence?
Lindström, T. M., & Robinson, W. H. (2010) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2010.02965.x · Cited by 122 · see citing works
Immunosenescence in Caenorhabditis elegans
Kim, S. S., Sohn, J., & Lee, S. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00314-8 · Cited by 19 · see citing works

Authors: Kovaiou, R. D., & Grubeck-Loebenstein, B.
Affiliations: Austrian Academy of Sciences (AT)
Venue: Immunology Letters
Publisher: Elsevier BV
Published: 2006-09
Volume: 107
Issue: 1
Pages: 8-14
ISSN: 0165-2478 (ISSN-L)
DOI: 10.1016/j.imlet.2006.07.006
OpenAlex: W2011939317
Cited by: 90
References: 81
Citations by year: 2026: 4 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 9 · 2012: 7
FWCI: 0.50
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Immunology Letters (publishedVersion)
PubMed (publishedVersion)
Funders: Austrian Science Fund
Oesterreichische Nationalbank
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: CD4+ T cells, immunosenescence, aging immune system, age-related immune dysfunction, vaccine response in the elderly, infection susceptibility, healthy aging, T cell dysfunction
MeSH terms: Aged, Aging, Antibody Formation, Humans, Immune Tolerance, Immunity, Cellular, Immunologic Memory, CD4-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

Age-associated changes within CD4+ T cells

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks