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

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-l-infected humans. In healthy, HIV-l-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/mu l per day and 6 CD8( +) T cells/mu l per day. In untreated HIV-l-infected subjects (with a mean CD4 level of 342 cells/mu l), the half-life of each subpopulation was less than 1/3 as long as those of healthy, HIV-l-seronegative subjects but was n ot compensated by an increased absolute production rate of CD4(+) T cells. After viral replication was suppressed by highly active antiretroviral ther apy for 12 weeks, the production rates of circulating CD4(+) and CD8(+) T c ells 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 circ ulating CD4(+) T cells. Our results focus attention on T-cell production sy stems in the pathogenesis of HIV-1 disease and the response to antiretrovir al therapy.