Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection.
Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.
Hellerstein
Marc K
MK
University of California, Berkeley, 119 Morgan Hall, Berkeley, California 94720-3104, USA. march@nature.berkeley.edu
Hoh
Rebecca A
RA
Hanley
Mary Beth
MB
Cesar
Denise
D
Lee
Daniel
D
Neese
Richard A
RA
McCune
Joseph M
JM
D019380:Anti-HIV Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D002470:Cell Survival; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003903:Deuterium / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007156:Immunologic Memory; D018655:Lymphocyte Count; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*
D019380:Anti-HIV Agents; D001786:Blood Glucose; D004247:DNA; D003903:Deuterium