CoChat
Sign Up
Cited by 1,073HIV Research and TreatmentT-cell and B-cell ImmunologyTelomeres, Telomerase, and Senescence

Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells

Brenchley, Jason M., Karandikar, Nitin J., Betts, Michael R., Ambrozak, David R., Hill, Brenna J., Crotty, Laura E., Casazza, Joseph P., Kuruppu, Janaki +5 more·2003·Blood
DOI 10.1182/blood-2002-07-2103
Open this paper in CoChat — free account

Abstract

Virus-specific CD8+ T-cell responses play a pivotal role in limiting viral replication. Alterations in these responses, such as decreased cytolytic function, inappropriate maturation, and limited proliferative ability could reduce their ability to control viral replication. Here, we report on the capacity of HIV-specific CD8+ T cells to secrete cytokines and proliferate in response to HIV antigen stimulation. We find that a large proportion of HIV-specific CD8+ T cells that produce cytokines in response to cognate antigen are unable to divide and die during a 48-hour in vitro culture. This lack of proliferative ability of HIV-specific CD8+ T cells is defined by surface expression of CD57 but not by absence of CD28 or CCR7. This inability to proliferate in response to antigen cannot be overcome by exogenous interleukin-2 (IL-2) or IL-15. Furthermore, CD57 expression on CD8+ T cells, CD4+ T cells, and NK cells is a general marker of proliferative inability, a history of more cell divisions, and short telomeres. We suggest, therefore, that the increase in CD57+ HIV-specific CD8+ T cells results from chronic antigen stimulation that is a hallmark of HIV infection. Thus, our studies define a phenotype associated with replicative senescence in HIV-specific CD8+ T cells, which may have broad implications to other conditions associated with chronic antigenic stimulation.

Integrity signals

Registry

Crossref · 10.1182/blood-2002-07-2103

Cites

70 of 70 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?

  • Terminally differentiated T cells do not express co-stimulatory molecules such as CD27 and CD28, but do express markers such as KLRG-1 and CD57, whose expression is largely overlapping.

    “they do not express co-stimulatory molecules such as CD27 and CD28, but do express markers such as KLRG-1 (a co-receptor bearing ITIM motif) and CD57 [337, 338], whose expression is largely overlapping.”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [337]

  • Terminally differentiated T cells display a reduced proliferative capacity, evidenced by telomeres shortening.

    “Terminally differentiated T cells display a reduced proliferative capacity, evidenced by telomeres shortening [337];”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [337]

  • High expression of Tim-3, CD57, and KLRG-1, in addition to low CD28, is thought to be associated with T cell senescence.

    “In addition to low expression of CD28, high expression of Tim-3, CD57, killer cell lectin-like receptor subfamily G, member 1 (KLRG-1) are thought to be associated with T cell senescence [40,60–64](Fig. 2).”

    From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [60]

  • Terminally differentiated T cells have limited proliferative capabilities and short telomeres, and are largely defined as approaching senescence.

    “However, terminally differentiated T cells are constrained by limited proliferative capabilities in tandem with short telomeres, and to a large extent, have been defined as approaching senescence [86, 87].”

    From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [87]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Brenchley, J. M., Karandikar, N. J., Betts, M. R., Ambrozak, D. R., Hill, B. J., Crotty, L. E., Casazza, J. P., Kuruppu, J., Migueles, S. A., Connors, M., Roederer, M., Douek, D. C., & Koup, R. A.
Affiliations
  • National Institutes of Health (US)
  • From the Vaccine Research Center and the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, MD; and the Departments of Pathology and Neurology, University of Texas, Southwestern Medical Center, Dallas.
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2003-04-01
Volume
101
Issue
7
Pages
2711-2720
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2002-07-2103
OpenAlex
W2158966732
Cited by
1,073
References
70
Citations by year
2026: 35 · 2025: 58 · 2024: 55 · 2023: 49 · 2022: 55 · 2021: 57 · 2020: 54 · 2019: 59 · 2018: 46 · 2017: 37 · 2016: 47 · 2015: 41 · 2014: 56 · 2013: 46 · 2012: 41
FWCI
14.44
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI047603, AI-49990, R01 AI 47603, K08AI049990)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Keywords
CD57, replicative senescence, CD8+ T cells, HIV-specific T cells, T cell proliferation, chronic antigenic stimulation, cytokine production, interleukin-2, IL-15, telomere shortening, natural killer cells, CD4+ T cells, virus control
MeSH terms
Cell Division, Humans, Lymphocyte Activation, Phenotype, HIV Antigens, HIV-1, Cytokines, Cellular Senescence, Apoptosis, CD28 Antigens, CD8-Positive T-Lymphocytes, CD57 Antigens, Receptors, Chemokine, Receptors, CCR7

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