Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection

J Clin Invest. 2003 Sep;112(6):956-66. doi: 10.1172/JCI17533.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / therapeutic use
  • Blood Glucose / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Survival
  • DNA / chemistry
  • DNA / metabolism
  • Deuterium / metabolism
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1*
  • Humans
  • Immunologic Memory*
  • Lymphocyte Count
  • Phenotype
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*

Substances

  • Anti-HIV Agents
  • Blood Glucose
  • DNA
  • Deuterium