Factors influencing T-cell turnover in HIV-1-seropositive patients.
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.
McCune
J M
JM
The Gladstone Institute of Virology and Immunology, University of California-San Francisco, San Francisco, California 94141, USA. mmccune@gladstone.ucsf.edu
Hanley
M B
MB
Cesar
D
D
Halvorsen
R
R
Hoh
R
R
Schmidt
D
D
Wieder
E
E
Deeks
S
S
Siler
S
S
Neese
R
R
Hellerstein
M
M
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002452:Cell Count; D002470:Cell Survival; D003903:Deuterium; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D013950:Thymus Gland / Q000473:pathology; D014057:Tomography, X-Ray Computed
D003903:Deuterium; D005947:Glucose