Augmentation of Apoptosis and Interferon-Gamma Production at Sites of Active Mycobacterium Tuberculosis Infection in Human Tuberculosis

J Infect Dis. 2001 Mar 1;183(5):779-88. doi: 10.1086/318817. Epub 2001 Feb 8.

Abstract

Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human immunodeficiency virus (HIV)-coinfected (HIV/TB) patients and patients infected with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluated. T cells were expanded at the site of MTB infection, irrespective of HIV status. Apoptosis of CD4 and non-CD4 T cells in the pleural space occurred in both HIV/TB and TB. Interferon (IFN)-gamma levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-gamma-producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor-alpha, Fas-ligand, and Fas, were increased in pleural fluid, compared with plasma. These data suggest that continued exposure of immunoreactive cells to MTB at sites of infection may initiate a vicious cycle in which immune activation and loss of antigen-responsive T cells occur concomitantly, thus favoring persistence of MTB infection.

Publication types

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

MeSH terms

  • AIDS-Related Opportunistic Infections / blood
  • AIDS-Related Opportunistic Infections / immunology*
  • AIDS-Related Opportunistic Infections / virology
  • Adolescent
  • Adult
  • Apoptosis / immunology*
  • CD4 Lymphocyte Count
  • Cells, Cultured
  • Cytokines
  • Fas Ligand Protein
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / virology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Tuberculosis, Pleural / blood
  • Tuberculosis, Pleural / immunology*
  • Tuberculosis, Pleural / virology
  • Tumor Necrosis Factor-alpha / analysis
  • Uganda

Substances

  • Cytokines
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma