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Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis
Abstract
OBJECTIVE: To test the hypothesis that the expanded population of non-proliferative CD28-CD8+ T cells in HIV disease have shortened telomeres, thereby providing evidence that increased rounds of CD8+ cell division occur during HIV disease, possibly leading to replicative senescence and exhaustion of CD8+ T-cell responses. DESIGN: CD8+ cells play a central role in control of HIV infection. In late HIV disease, an expanded population of CD28-CD8+ cells with reduced proliferative potential has been documented. A similar population of CD28-CD8+ cells has been identified in ageing humans, where telomere length measurements have suggested that these cells have reached the irreversible state of replicative senescence. METHODS: CD8+ cells from HIV-infected and control subjects were sorted by flow cytometry into CD28+ and CD28- fractions. Telomere lengths were determined as mean terminal restriction fragment (TRF) lengths by Southern hybridization. RESULTS: The TRF lengths of sorted CD28-CD8+ cells in HIV-infected subjects ranged between 5 and 7 kilobases (kb) and were significantly shorter than TRF lengths of CD28-CD8+ cells in uninfected subjects (P = 0.003). The TRF length in CD28-CD8+ cells from HIV-infected subjects was the same as that observed for centenarian peripheral blood mononuclear cells and is compatible with a state of replicative senescence. CONCLUSIONS: The shortened telomeres in the CD28-CD8+ cells in HIV-infected subjects and the poor proliferative potential of these cells identifies CD8+ cell replicative senescence as a newly described feature of HIV disease. Our results provide a mechanism for the loss of CD8+ cell control of viral replication that accompanies advanced HIV disease. Replicative senescence may contribute to exhaustion of the T-cell response as a result of chronic HIV disease. Whether this phenomenon occurs in other chronic viral infections is unknown.
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“Interestingly, certain hallmarks of cellular senescence are also found in T cells from patients with HIV (Effros et al, 1996; Wolthers et al, 1996; Palmer et al, 1997; Nelson et al, 2012; Pereira Ribeiro et al, 2016).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Effros et al, 1996
In the citing paper
“Telomere lengths of CD8+ T cells are shorter in HIV patients compared to healthy individuals, but this observation was not found in CD4+ T cells.”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Effros et al, 1996
In the citing paper
“Telomere lengths of CD8+ T cells are shorter in HIV patients compared to healthy individuals, but this observation was not found in CD4+ T cells.”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Effros et al, 1996
In the citing paper
“These finds were also independent on whether HIV patients were on antiretroviral therapy (Effros et al, 1996; Wolthers et al, 1996; Palmer et al, 1997).”
From The struggle of a good friend getting old: cellular senescence in viral responses and therapy (2021) · cites this paper as Effros et al, 1996
In the citing paper
“As previously reported for replicatively senescent CD8 + T lymphocytes (23,26,27), the CD28 -CD57 + subset had shortened telomeres and showed an increase in cells positive for senescence-associated β-galactosidase (SA-β-gal) compared with the CD28 + CD57 -subset (Figure 1, B and C, and Supplemental Figure 3).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [26]
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Metadata
- Authors
- Effros, R. B., Allsopp, R., Chiu, C.-P., Hausner, M. A., Hirji, K., Wang, L., Harley, C. B., Villeponteau, B., West, M. D., & Giorgi, J. V.
- Affiliations
- University of California, Los Angeles (US)
- Venue
- AIDS
- Published
- 1996-07
- Volume
- 10
- Issue
- 8
- Pages
- F17-22
- ISSN
- 0269-9370 (ISSN-L)
- OpenAlex
- W1988707875
- Cited by
- 457
- References
- 0
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 15 · 2020: 4 · 2019: 10 · 2018: 13 · 2017: 13 · 2016: 10 · 2015: 15 · 2014: 12 · 2013: 15 · 2012: 19
- FWCI
- 9.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- AIDS (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ai032883-05)
- National Institute of Allergy and Infectious Diseases (U01AI035040, AI-32883, AI-28 697, P30AI028697, AI35040)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- telomere shortening, replicative senescence, HIV infection, CD8+ T cell exhaustion, T cell proliferation, chronic viral infection, immunosenescence
- MeSH terms
- Cell Division, DNA, Humans, Molecular Weight, HIV Infections, T-Lymphocyte Subsets, Telomere, Cellular Senescence, CD28 Antigens, CD8-Positive T-Lymphocytes
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