Augmentation of Apoptosis and Interferon-g Production at sites of active Mycobacterium Tuberculosis infection in Human Tuberculosis

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)–g levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-g–producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor–a, 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 antigenresponsive T cells occur concomitantly, thus favoring persistence of MTB infection.