T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4 + T Cell Turnover

Wolthers, Katja C.; Bea, G.; Wisman, A.; Otto, Sigrid A.; de Roda Husman, Ana-Maria; Schaft, Niels; de Wolf, Frank; Goudsmit, Jaap; Coutinho, Roel A.; van der Zee, Ate G. J.; Meyaard, Linde; Miedema, Frank

doi:10.1126/science.274.5292.1543

Cited by 287HIV Research and TreatmentTelomeres, Telomerase, and SenescenceT-cell and B-cell Immunology

T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4 + T Cell Turnover

Wolthers, Katja C., Bea, G., Wisman, A., Otto, Sigrid A., de Roda Husman, Ana-Maria, Schaft, Niels, de Wolf, Frank, Goudsmit, Jaap +4 more·1996·Science

DOI 10.1126/science.274.5292.1543

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Abstract

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8 + T cell TRF length decreased but CD4 + T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8 + T cells, but not in CD4 + T cells. These results are compatible with CD4 + T cell decline in HIV-1 infection caused by interference with cell renewal.

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The shorter telomere lengths in CD8+ T cells in HIV patients are independent of antiretroviral therapy status.
“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 Wolthers et al, 1996
Certain hallmarks of cellular senescence are found in T cells from HIV patients.
“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 Wolthers et al, 1996
CD8+ T cell telomere lengths are shorter in HIV patients compared to healthy individuals.
“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 Wolthers et al, 1996
CD4+ T cell telomere lengths are not shorter in HIV patients compared to healthy individuals.
“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 Wolthers et al, 1996

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Analysis of telomere length and thymic output in fast and slow/non-progressors with HIV infection
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Authors: Wolthers, K. C., Bea, G., Wisman, A., Otto, S. A., de Roda Husman, A.-M., Schaft, N., de Wolf, F., Goudsmit, J., Coutinho, R. A., van der Zee, A. G. J., Meyaard, L., & Miedema, F.
Affiliations: University of Amsterdam (NL)
University Medical Center Groningen (NL)
K. C. Wolthers, S. A. Otto, A.-M. de Roda Husman, N. Schaft, L. Meyaard, Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology of the University of Amsterdam, Amsterdam, Netherlands.
F. de Wolf and J. Goudsmit, Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
Amsterdam UMC Location University of Amsterdam (NL)
GGD Amsterdam (NL)
G. B. A. Wisman and A. G. J. van der Zee, Department of Gynaecology and Obstetrics, Academic Hospital Groningen, University of Groningen, Groningen, Netherlands.
Corresponding author: Miedema, Frank
ORCID: Wolthers, Katja C.
Schaft, Niels
Meyaard, Linde
Miedema, Frank
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-11-29
Volume: 274
Issue: 5292
Pages: 1543-1547
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.274.5292.1543
OpenAlex: W2055875053
Cited by: 286
References: 58
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 7 · 2015: 2 · 2014: 6 · 2013: 8 · 2012: 5
FWCI: 8.82
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: HIV-1 infection, telomere length, terminal restriction fragments, CD4+ T cells, CD8+ T cells, T cell turnover, telomerase activity, immunosenescence, AIDS progression
MeSH terms: Acquired Immunodeficiency Syndrome, Cell Division, Cross-Sectional Studies, Humans, Leukocytes, Mononuclear, Male, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Matched-Pair Analysis, Telomere, Cell Death, CD8-Positive T-Lymphocytes, Disease Progression, Lymphocyte Count, CD4 Lymphocyte Count, Telomerase

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T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4 + T Cell Turnover

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