Apoptosis and T Cell Hyporesponsiveness in Pulmonary Tuberculosis

J Infect Dis. 1999 Apr;179(4):945-53. doi: 10.1086/314667.

Abstract

Mycobacterium tuberculosis (MTB)-induced T cell responses are depressed in peripheral blood mononuclear cells of persons with newly diagnosed pulmonary tuberculosis (TB), and levels of interferon (IFN)-gamma remain low even after completion of antituberculous therapy. Loss of MTB-reactive T cells through apoptotic mechanisms could account for this prolonged T cell hyporesponsiveness. T cell apoptosis was studied in TB patients and healthy control subjects. Both spontaneous and MTB-induced apoptosis (in CD4 and non-CD4 T cells) from TB patients was increased when compared with healthy control subjects, whereas coculture with control antigen (candida) had no effect on T cell apoptosis in either group of study subjects. An inverse correlation existed between increased MTB-induced T cell apoptosis and IFN-gamma and interleukin (IL)-2 immunoreactivities. Successful antituberculous chemotherapy resulted in a 50% reduction in both spontaneous and MTB-induced apoptosis, which coincided with 3- and 8-fold increases in levels of MTB-stimulated IL-2 and IFN-gamma, respectively. These data indicate that apoptotic pathways are operant during active MTB infection and may contribute to deletion of MTB-reactive T cells and the immunopathogenesis of this disease.

Publication types

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

MeSH terms

  • Apoptosis*
  • CD4 Lymphocyte Count
  • Epitopes
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / analysis
  • Interleukin-2 / biosynthesis
  • T-Lymphocytes / immunology*
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / pathology

Substances

  • Epitopes
  • Interleukin-2
  • Interferon-gamma