title: Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans.
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/microl per day and 6 CD8+ T cells/microl per day. In untreated HIV-1-infected subjects (with a mean CD4 level of 342 cells/microl), 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.
authors.affiliation: Department of Medicine, San Francisco General Hospital, University of California at San Francisco, 94110, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hellerstein
authors.forename: M B
authors.initials: MB
authors.lastname: Hanley
authors.forename: D
authors.initials: D
authors.lastname: Cesar
authors.forename: S
authors.initials: S
authors.lastname: Siler
authors.forename: C
authors.initials: C
authors.lastname: Papageorgopoulos
authors.forename: E
authors.initials: E
authors.lastname: Wieder
authors.forename: D
authors.initials: D
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Hoh
authors.forename: R
authors.initials: R
authors.lastname: Neese
authors.forename: D
authors.initials: D
authors.lastname: Macallan
authors.forename: S
authors.initials: S
authors.lastname: Deeks
authors.forename: J M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008297:Male