Changes in thymic function with age and during the treatment of HIV infection

Douek, Daniel C.; McFarland, Richard D.; Keiser, Philip H.; Gage, Earl A.; Massey, Janice M.; Haynes, Barton F.; Polis, Michael A.; Haase, Ashley T.; Feinberg, Mark B.; Sullivan#, John L.; Jamieson, Beth D.; Zack, Jerome A.; Picker, Louis J.; Koup, Richard A.

doi:10.1038/25374

Cited by 1,893HIV Research and TreatmentT-cell and B-cell ImmunologyHIV-related health complications and treatments

Changes in thymic function with age and during the treatment of HIV infection

Douek, Daniel C., McFarland, Richard D., Keiser, Philip H., Gage, Earl A., Massey, Janice M., Haynes, Barton F., Polis, Michael A., Haase, Ashley T. +6 more·1998·Nature

DOI 10.1038/25374

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Abstract

The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.

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Thymic output persists, albeit reduced, up until around 70 years of age.
“While studies continue to support the age-associated reduction in thymic function, evidence now points towards a more gradual decline, whereby thymic output persists, albeit reduced, up until around 70 years of age (Douek et al. 1998; Ferrando-Martinez et al. 2010).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Douek et al. 1998

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“…of highly active antiretroviral therapy, which has prolonged the survival of these patients despite a persistent inflammation, fueled by high levels of IL-6 and TNF-α , interferon (IFN)- α , reduced production of IL-2 [116–118], as well as by a variable decrease in the number of TRECs [37,119,120].”
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Authors: Douek, D. C., McFarland, R. D., Keiser, P. H., Gage, E. A., Massey, J. M., Haynes, B. F., Polis, M. A., Haase, A. T., Feinberg, M. B., Sullivan#, J. L., Jamieson, B. D., Zack, J. A., Picker, L. J., & Koup, R. A.
Affiliations: The University of Texas Southwestern Medical Center (US)
Duke Medical Center (US)
National Institutes of Health (US)
University of Minnesota (US)
Emory University (US)
University of California, Los Angeles (US)
Corresponding author: Koup, Richard A.
ORCID: Douek, Daniel C.
Massey, Janice M.
Haynes, Barton F.
Polis, Michael A.
Haase, Ashley T.
Feinberg, Mark B.
Jamieson, Beth D.
Zack, Jerome A.
Picker, Louis J.
Koup, Richard A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1998-12
Volume: 396
Issue: 6712
Pages: 690-695
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/25374
OpenAlex: W1580217007
Cited by: 1,893
References: 28
Citations by year: 2026: 36 · 2025: 32 · 2024: 25 · 2023: 23 · 2022: 24 · 2021: 39 · 2020: 35 · 2019: 71 · 2018: 44 · 2017: 48 · 2016: 55 · 2015: 51 · 2014: 71 · 2013: 76 · 2012: 72
FWCI: 29.52
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
eScholarship@UMassChan (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
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 › Emergency Medicine › HIV-related health complications and treatments
Keywords: thymic function, thymic output, HIV infection, aging, thymic involution, highly active antiretroviral therapy, naive CD4+ T cells, T-cell receptor gene rearrangement, immune reconstitution, thymus
MeSH terms: Adolescent, Adult, Aged, Aging, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Middle Aged, Receptors, Antigen, T-Cell, Thymus Gland, Gene Rearrangement, T-Lymphocyte, Cohort Studies, CD4-Positive T-Lymphocytes, HIV Infections, Case-Control Studies, Polymerase Chain Reaction, CD8-Positive T-Lymphocytes, Leukopoiesis

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Changes in thymic function with age and during the treatment of HIV infection

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