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, E. Wieder, D. Schmidt, R. Hoh, R. Neese, D. Macallan, S. Deeks, J. M. Mccune

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hellerstein, M., Hanley, M. B., Cesar, D., Siler, S., Papageorgopoulos, C., Wieder, E., Schmidt, D., Hoh, R., Neese, R., Macallan, D., Deeks, S., & 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