Cited by 431

The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.

CD28 extinction in human T cells: altered functions and the program of T‐cell senescence

Vallejo, Abbe N.·2005·Immunological Reviews

DOI 10.1111/j.0105-2896.2005.00256.x

Open this paper in CoChat — free account

Abstract

Summary: The loss of CD28 expression on T cells is the most consistent biological indicator of aging in the human immune system, and the frequency of CD28 null T cells is a key predictor of immune incompetence in the elderly. There is also mounting evidence for the high frequency of these unusual T cells among patients with inflammatory syndromes or with chronic infections disproportionate with their age. In these pathological states, CD28 null T cells likely represent prematurely senescent lymphocytes due to persistent immune activation. Unlike the situation in CD28 gene knockout mice that have anergic CD28 0/0 T cells, human CD28 null T cells are functionally active, long‐lived, oligoclonal lymphocytes that lack or have limited proliferative capacity. Results of replicative senescence studies show that CD28 null T cells are derived from CD28+ precursors that have undergone repeated stimulation, indicating that CD28 silencing underlies the program of T‐cell aging. Dissection of the machinery regulating CD28 expression is paving the way in elucidating the molecular events leading to immune senescence as well as providing clues into the functional rejuvenation of senescent T cells.

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 · 10.1111/j.0105-2896.2005.00256.x

Cites

18 of 18 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.

Self-check

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

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

CD28/B7 SYSTEM OF T CELL COSTIMULATION
Lenschow, D. J., Walunas, T. L., & Bluestone, J. A. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.233 · Cited by 2,717
HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function
Appay, V., Nixon, D. F., Donahoe, S. M., Gillespie, G. M. A., Dong, T., King, A., Ogg, G. S., Spiegel, H. M. L., Conlon, C., Spina, C. A., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.1.63 · Cited by 871
CD28-mediated co-stimulation: a quantitative support for TCR signalling.
Acuto, O., & Michel, F. (2003) · Nature Reviews Immunology · doi:10.1038/nri1248 · Cited by 775
Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines
Saurwein-Teissl, M., Lung, T. L., Marx, F., Gschösser, C., Asch, E., Blasko, I., Parson, W., Böck, G., Schönitzer, D., Trannoy, E., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5893 · Cited by 499
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
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
Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts
Monteiro, J., Batliwalla, F., Ostrer, H., & Gregersen, P. K. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.10.3587 · Cited by 376
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
Self-citation
Resistance to apoptosis in human CD8+ T cells that reach replicative senescence after multiple rounds of antigen-specific proliferation☆
Spaulding, C., Guo, W., & Effros, R. B. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00033-9 · Cited by 258
T-cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection
Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.01.002 · Cited by 223
Self-citation

Show all 18 references

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
CD8+ CD28− and CD8+ CD57+ T cells and their role in health and disease: CD8+ CD28− (CD8+ CD57+) T cells in health and disease
Strioga, M., Pasukoniene, V., & Characiejus, D. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03470.x · Cited by 505
Immunology of aging: the birth of inflammaging
Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A. A., Hirokawa, K., Witkowski, J. M., & Franceschi, C. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08899-6 · Cited by 464
The immune system and aging: A review
Castelo-Branco, C., & Soveral, I. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2013.852531 · Cited by 449
Immunosenescence in aging: Between immune cells depletion and cytokines up-regulation
Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017) · Clinical and Molecular Allergy · doi:10.1186/s12948-017-0077-0 · Cited by 389
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Zhao, Y., Shao, Q., & Peng, G. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0344-8 · Cited by 382
Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade
Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M. E., Kaminski, M., Gostick, E., Price, D. A., Freeman, G. J., Wherry, E. J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000313 · Cited by 380
Inflammaging decreases adaptive and innate immune responses in mice and humans
Frasca, D., & Blomberg, B. B. (2016) · Biogerontology · doi:10.1007/s10522-015-9578-8 · Cited by 357
The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells
Lanna, A., Henson, S. M., Escors, D., & Akbar, A. N. (2014) · Nature Immunology · doi:10.1038/ni.2981 · Cited by 328
Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease
Nielsen, C. M., White, M. J., Goodier, M. R., & Riley, E. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00422 · Cited by 282
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition
Liu, X., Mo, W., Ye, J., Li, L., Zhang, Y., Hsueh, E. C., Hoft, D. F., & Peng, G. (2018) · Nature Communications · doi:10.1038/s41467-017-02689-5 · Cited by 224
The loss of telomerase activity in highly differentiated CD8+CD28−CD27− T cells is associated with decreased Akt (Ser473) phosphorylation
Plunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., & Akbar, A. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7710 · Cited by 222
The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology
Huff, W. X., Kwon, J. H., Henriquez, M., Fetcko, K., & Dey, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112810 · Cited by 217
Role of CMV in immune senescence.
Pawelec, G., & Derhovanessian, E. (2011) · Virus Research · doi:10.1016/j.virusres.2010.09.010 · Cited by 201
Tumor-Derived γδ Regulatory T Cells Suppress Innate and Adaptive Immunity through the Induction of Immunosenescence
Ye, J., Ma, C., Hsueh, E. C., Eickhoff, C. S., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202369 · Cited by 203
Human regulatory T cells induce T-lymphocyte senescence
Ye, J., Huang, X., Hsueh, E. C., Zhang, Q., Ma, C., Zhang, Y., Varvares, M. A., Hoft, D. F., & Peng, G. (2012) · Blood · doi:10.1182/blood-2012-03-416040 · Cited by 198
Immunosenenescence: role of cytomegalovirus
Pawelec, G. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.010 · Cited by 163
TLR8 signaling enhances tumor immunity by preventing tumor‐induced T‐cell senescence
Ye, J., Ma, C., Hsueh, E. C., Dou, J., Mo, W., Liu, S., Han, B., Huang, Y., Zhang, Y., Varvares, M. A., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201403918 · Cited by 161
Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration
Lee, K. S., Lin, S., Copland, D. A., Dick, A. D., & Liu, J. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02088-0 · Cited by 150
Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans
Frasca, D., Diaz, A., Romero, M., Landin, A. M., Phillips, M., Lechner, S. C., Ryan, J. G., & Blomberg, B. B. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.10.023 · Cited by 143
The Role of Immunosenescence in Neurodegenerative Diseases
Costantini, E., D’Angelo, C., & Reale, M. (2018) · Mediators of Inflammation · doi:10.1155/2018/6039171 · Cited by 133
Tumor-induced senescent T cells with suppressor function: a potential form of tumor immune evasion
Montes, C. L., Chapoval, A. I., Nelson, J., Orhue, V., Zhang, X., Schulze, D. H., Strome, S. E., & Gastman, B. R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2282 · Cited by 127
Metabolic reprogramming of human CD8+ memory T cells through loss of SIRT1
Jeng, M. Y., Hull, P. A., Fei, M., Kwon, H.-S., Tsou, C.-L., Kasler, H., Ng, C.-P., Gordon, D. E., Johnson, J., Krogan, N., et al. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20161066 · Cited by 121
High TNF-α levels in resting B cells negatively correlate with their response
Frasca, D., Diaz, A., Romero, M., Landin, A. M., & Blomberg, B. B. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.01.004 · Cited by 115
“T cells (Lazuardi et al., 2005; Pawelec et al., 2009; Vallejo, 2005) and innate cells (Panda et al., 2010; Solana et al., 2006; Sridharan et al., 2010) have decreased function with age.”
Impact of age on T cell signaling: A general defect or specific alterations?
Larbi, A., Pawelec, G., Wong, S. C., Goldeck, D., Tai, J. J.-Y., & Fulop, T. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2010.09.008 · Cited by 108
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
Challenges in glioblastoma immunotherapy: mechanisms of resistance and therapeutic approaches to overcome them
Habashy, K. J., Mansour, R., Moussalem, C., Sawaya, R., & Massaad, M. J. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01864-w · Cited by 95
The Impact of Aging on Regulatory T-Cells
Fessler, J., Ficjan, A., Duftner, C., & Dejaco, C. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00231 · Cited by 88
Age-associated changes within CD4+ T cells
Kovaiou, R. D., & Grubeck-Loebenstein, B. (2006) · Immunology Letters · doi:10.1016/j.imlet.2006.07.006 · Cited by 90
Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
Merani, S., Pawelec, G., Kuchel, G. A., & McElhaney, J. E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00784 · Cited by 74
Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in “human immune system” Rag2-/-γc-/- mice
Legrand, N., Cupedo, T., van Lent, A. U., Ebeli, M. J., Weijer, K., Hanke, T., & Spits, H. (2006) · Blood · doi:10.1182/blood-2006-01-0190 · Cited by 82
Immunosenescence is associated with human cytomegalovirus and shortened telomeres in type I bipolar disorder
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
Age-associated up-regulation of a negative co-stimulatory receptor PD-1 in mouse CD4+ T cells
Shimada, Y., Hayashi, M., Nagasaka, Y., Ohno-Iwashita, Y., & Inomata, M. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.05.003 · Cited by 72
MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals
Frasca, D., Diaz, A., Romero, M., Ferracci, F., & Blomberg, B. B. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500520 · Cited by 69
Accumulation of 4-1BBL+ B cells in the elderly induces the generation of granzyme-B+ CD8+ T cells with potential antitumor activity
Lee-Chang, C., Bodogai, M., Moritoh, K., Olkhanud, P. B., Chan, A. C., Croft, M., Mattison, J. A., Holst, P. J., Gress, R. E., Ferrucci, L., et al. (2014) · Blood · doi:10.1182/blood-2014-03-563940 · Cited by 58
Optimal window of caloric restriction onset limits its beneficial impact on T‐cell senescence in primates
Messaoudi, I., Fischer, M., Warner, J., Park, B., Mattison, J., Ingram, D. K., Totonchy, T., Mori, M., & Nikolich‐Žugich, J. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00440.x · Cited by 57
Aging, cytomegalovirus (CMV) and influenza vaccine responses
Frasca, D., & Blomberg, B. B. (2016) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2015.1105413 · Cited by 46
Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery
Fornara, O., Odeberg, J., Wolmer Solberg, N., Tammik, C., Skarman, P., Peredo, I., Stragliotto, G., Rahbar, A., & Söderberg-Nauclér, C. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1036211 · Cited by 45
Systemic hypoxia promotes lymphocyte apoptosis induced by oxidative stress during moderate exercise
Wang, J.-S., & Lin, C.-T. (2010) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1231-2 · Cited by 29
Age-Dependent Association between Low Frequency of CD27/CD28 Expression on pp65 CD8+T Cells and Cytomegalovirus Replication after Transplantation
Cantisán, S., Torre-Cisneros, J., Lara, R., Rodríguez-Benot, A., Santos, F., Gutiérrez-Aroca, J., Gayoso, I., González-Padilla, M., Casal, M., Rivero, A., et al. (2009) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00214-09 · Cited by 27
Age-Related Adaptive Immune Changes in Parkinson’s Disease
Kouli, A., & Williams-Gray, C. H. (2022) · Journal of Parkinson's Disease · doi:10.3233/jpd-223228 · Cited by 20
Nutraceuticals in immunosenescence
Magrone, T., & Jirillo, E. (2015) · Anti‐ageing nutrients · doi:10.1002/9781118823408.ch5 · Cited by 4

Authors: Vallejo, A. N.
Venue: Immunological Reviews
Publisher: Wiley
Published: 2005-05-09
Volume: 205
Issue: 1
Pages: 158-169
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/j.0105-2896.2005.00256.x
OpenAlex: W2075372159
Cited by: 431
References: 18
FWCI: 0.65
Type: journal article
Language: en
Open access: closed

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

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.

CD28 extinction in human T cells: altered functions and the program of T‐cell senescence

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Metadata

Record

About these checks

Data sources