Granule-dependent cytolysis of Mycobacterium tuberculosis-infected macrophages by human gamma delta(+) T cells has no effect on intracellular mycobacterial viability

One of the most important effector functions of activated gamma delta (+) T cells in tuberculosis is their strong cytolytic activity against a variety of target cells, including M. tuberculosis-infected macrophages. In the pr esent study, we investigated the relationship between the mechanism of cyto lysis utilized by gamma delta (+) CTL and intracellular M. tuberculosis sur vival using a panel of cytolytic human M. tuberculosis-specific gamma delta (+) CTL clones. Cytolysis mediated by the gamma delta (+) T-cell clones wa s found to be Ca2+-dependent, sensitive to Cyclosporin A, and was completel y abrogated following Sr2+-induced de-granulation of the gamma delta (+) T cell effectors. These data demonstrate that gamma delta (+) T-cell-mediated cytoxicity was mediated via the granule exocytosis/perforin pathway. Despi te significant cytolytic activity against mycobacteria infected U937 cells, the gamma delta (+) CTL clones had no impact on the survival of intracellu lar M. tuberculosis.