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

M Hellerstein, MB Hanley, D Cesar, S Siler… - Nature medicine, 1999 - nature.com
M Hellerstein, MB Hanley, D Cesar, S Siler, C Papageorgopoulos, E Wieder, D Schmidt…
Nature medicine, 1999nature.com
The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial.
Using a new, non-radioactive, endogenous labeling technique 1, 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 …
Abstract
The dynamic basis for T-cell depletion in late-stage HIV-1 disease remains controversial. Using a new, non-radioactive, endogenous labeling technique 1, 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.
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