Apoptosis and T cell hyporesponsiveness in pulmonary tuberculosis

Mycobacterium tuberculosis (MTB)-induced T cell responses are depressed in peripheral blood mononuclear cells of persons with newly diagnosed pulmonar y tuberculosis (TB), and levels of interferon (IFN)-gamma remain low even a fter completion of antituberculous therapy. Loss of MTB-reactive T cells th rough apoptotic mechanisms could account for this prolonged T cell hyporesp onsiveness, 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 s ubjects, 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 in terleukin Ca immunoreactivities. Successful antituberculous chemotherapy re sulted in a 50% reduction in both spontaneous and MTB-induced apoptosis, wh ich coincided with 3- and 8-fold increases in levels of MTB-stimulated IL-2 and IFN-gamma, respectively. These data indicate that apoptotic pathways a re operant during active MTB infection and may contribute to deletion of MT B-reactive T cells and the immunopathogenesis of this disease.