Augmentation of apoptosis and Interferon-gamma production at sites of active mycobacterium tuberculosis infection in human tuberculosis

Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human imm unodeficiency virus (HIV)-coinfected (HIV/TB) patients and patients infecte d with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluat ed. 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 ple ural fluid, compared with plasma. Spontaneous apoptosis correlated with spe cific loss of MTB-reactive, IFN-gamma -producing pleural T cells. Immunorea ctivities of molecules potentially involved in apoptosis, such as tumor nec rosis factor-alpha, Fas-ligand, and Fas, were increased in pleural fluid, c ompared with plasma. These data suggest that continued exposure of immunore active cells to MTB at sites of infection may initiate a vicious cycle in w hich immune activation and loss of antigen-responsive T cells occur concomi tantly, thus favoring persistence of MTB infection.