Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans

M. Hellerstein, M. B. Hanley, D. Cesar, S. Siler, C. Papageorgopoulos, Eric Wieder, D. Schmidt, R. Hoh, R. Neese, D. Macallan, S. Deeks, J. M. Mccune

Research output: Contribution to journalArticle

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Abstract

The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique, we report direct measurements of circulating T-cell kinetics in normal and in HIV-1-infected humans. In healthy, HIV-1-seronegative subjects, CD4+ and CD8+ T cells had half-lives of 87 days and 77 days, respectively, with absolute production rates of 10 CD4+ T cells/μl per day and 6 CD8+ T cells/μl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/μl), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-1-seronegative subjects but was not compensated by an increased absolute production rate of CD4+ T cells. After viral replication was suppressed by highly active antiretroviral therapy for 12 weeks, the production rates of circulating CD4+ and CD8+ T cells were considerably elevated; the kinetic basis of increased CD4 levels was greater production, not a longer half-life, of circulating cells. These direct measurements indicate that CD4+ T-cell lymphopenia is due to both a shortened survival time and a failure to increase the production of circulating CD4+ T cells. Our results focus attention on T-cell production systems in the pathogenesis of HIV-1 disease and the response to antiretroviral therapy.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalNature Medicine
Volume5
Issue number1
DOIs
StatePublished - Feb 2 1999
Externally publishedYes

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T-cells
HIV-1
T-Lymphocytes
Kinetics
Half-Life
Lymphopenia
Highly Active Antiretroviral Therapy
Labeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Hellerstein, M., Hanley, M. B., Cesar, D., Siler, S., Papageorgopoulos, C., Wieder, E., ... Mccune, J. M. (1999). Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nature Medicine, 5(1), 83-89. https://doi.org/10.1038/4772

Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. / Hellerstein, M.; Hanley, M. B.; Cesar, D.; Siler, S.; Papageorgopoulos, C.; Wieder, Eric; Schmidt, D.; Hoh, R.; Neese, R.; Macallan, D.; Deeks, S.; Mccune, J. M.

In: Nature Medicine, Vol. 5, No. 1, 02.02.1999, p. 83-89.

Research output: Contribution to journalArticle

Hellerstein, M, Hanley, MB, Cesar, D, Siler, S, Papageorgopoulos, C, Wieder, E, Schmidt, D, Hoh, R, Neese, R, Macallan, D, Deeks, S & Mccune, JM 1999, 'Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans', Nature Medicine, vol. 5, no. 1, pp. 83-89. https://doi.org/10.1038/4772
Hellerstein M, Hanley MB, Cesar D, Siler S, Papageorgopoulos C, Wieder E et al. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nature Medicine. 1999 Feb 2;5(1):83-89. https://doi.org/10.1038/4772
Hellerstein, M. ; Hanley, M. B. ; Cesar, D. ; Siler, S. ; Papageorgopoulos, C. ; Wieder, Eric ; Schmidt, D. ; Hoh, R. ; Neese, R. ; Macallan, D. ; Deeks, S. ; Mccune, J. M. / Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. In: Nature Medicine. 1999 ; Vol. 5, No. 1. pp. 83-89.
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