Mycobacterium tuberculosis infection of human monocyte-derived macrophages leads to apoptosis of T cells.

The induction of apoptosis of T cells by intracellular pathogen is an attractive hypothesis to explain their persistence in host cells. To test this hypothesis, human monocyte-derived macrophages were infected with Mycobacterium tuberculosis H37Rv and cocultured with autologous T cells stimulated with nonspecific phytohemagglutinin (PHA) or specific culture filtrate protein (CFP) of M. tuberculosis. CD95 (Fas) expression, propidium iodide (PI) staining and terminal deoxy nucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay of CD3 cells were studied to assess the viability. Apoptotic cells were correlated with the levels of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). An increased CD3/PI and CD3/CD95(+) PHA-preactivated T cells in coculture with M. tuberculosis-infected macrophages suggested Fas-Fas ligand interactions to be important in apoptosis of nonspecifically stimulated T cells. Significantly higher NO and TNF- alpha levels suggested an association of the soluble factors with apoptosis of nonspecifically activated T cells. Significantly high release of TNF-alpha in the coculture of infected macrophages with CFP-activated T cells pointed toward its association with specific T-cell apoptosis. We show for the first time that in vitro infection of human macrophages with M. tuberculosis induces apoptosis of specific and to a much greater extent of nonspecific T cells.