Cell Cycling in HIV Infection: Analysis of in Vivo Activated Lymphocytes

Clin Exp Immunol. 1995 Dec;102(3):481-6. doi: 10.1111/j.1365-2249.1995.tb03841.x.

Abstract

Infection with HIV results in increased circulating levels of T lymphocytes expressing phenotypic markers of immune activation. In the present study, using three-colour immunofluorescence, we examined the cell cycle status of these activated cells. Activated (HLA-DR+, CD25+ and CD38+) CD4+ and CD8+ T lymphocytes in peripheral blood were analysed for DNA content in 15 HIV+ patients and 10 healthy age- and sex-matched control subjects. As expected, all HIV+ patients had elevated percentage levels of activated CD4+ HLA-DR+, CD4+ CD25+, CD8+ HLA-DR+, CD8+ CD25+ and CD8+ CD38+ T lymphocytes compared with control subjects (P < 0.001 for all). Percentage levels of CD4+ HLA-DR+ and CD8+ HLA-DR+T lymphocytes in the 'proliferative' (S-G2M) phase of the cell cycle were also higher in the HIV+ patients compared with controls (P < 0.001 for both). The percentage levels of proliferative CD4+ CD25+, CD8+ CD25+ and CD8+ CD38+ lymphocytes were, however, similar in HIV+ patients and controls, indicating that the proliferative fraction of cells in vivo was confined to the HLA-DR+ subset and absent from the CD25+ and CD38+ populations. Four HIV+ patients had grossly elevated levels of CD8+ lymphocytes which were CD38+ (> 95%) and confined to the pre-G0-G1 phase of the cell cycle, suggesting these may be cells committed to apoptosis. These observations indicate an increase in the proliferative capacity of HLA-DR+ T lymphocytes in HIV infection in vivo. The reduced DNA content in other populations (e.g. CD38+ CD8+ lymphocytes) of some patients with advanced HIV disease suggests that these cells are apoptotic. Thus our results define both proliferative and apoptotic processes as a spectrum of activation-related events in HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adult
  • Antigens, CD*
  • Antigens, Differentiation / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Cycle
  • Female
  • HIV Infections / immunology*
  • HLA-DR Antigens / analysis
  • Humans
  • Lymphocyte Activation*
  • Male
  • Membrane Glycoproteins
  • N-Glycosyl Hydrolases / analysis
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • HLA-DR Antigens
  • Membrane Glycoproteins
  • N-Glycosyl Hydrolases
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1