HIV-1 disease is associated with pathological effects on T-cell production, destruction, and distribution. Using the deuterated (2H) glucose method for endogenous labeling, we have analyzed host factors that influence T-cell turnover in HIV-1–uninfected and –infected humans. In untreated HIV-1 disease, the average half life of circulating T cells was diminished without compensatory increases in cell production. Within 12 weeks of the initiation of highly active antiretroviral therapy (HAART), the absolute production rates of circulating T cells increased, and normal half-lives and production rates were restored by 12–36 months. Interpatient heterogeneity in the absolute degree of turnover correlated with the relative proportion of naive- and memory/effector-phenotype T cells in each of the CD4+ and CD8+ populations. The half-lives of naive-phenotype T cells ranged from 116–365 days (fractional replacement rates of 0.19–0.60% per day), whereas memory/effector-phenotype T cells persisted with half-lives from 22–79 days (fractional replacement rates of 0.87–3.14% per day). Naive-phenotype T cells were more abundant, and the half-life of total T cells was prolonged in individuals with abundant thymic tissue, as assessed by computed tomography. Such interpatient variation in T-cell kinetics may be reflective of differences in functional immune reconstitution after treatment for HIV-1 disease.
Joseph M. McCune, Mary Beth Hanley, Denise Cesar, Robert Halvorsen, Rebecca Hoh, Diane Schmidt, Eric Wieder, Steven Deeks, Scott Siler, Richard Neese, Marc Hellerstein
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