V gamma 9/V delta 2 T lymphocytes reduce the viability of intracellular Mycobacterium tuberculosis

An effective immune response against the intracellular pathogen Mycobacterium tuberculosis is strictly dependent on T cell activation. Although this protective response mainly depends on local release of pro-inflammatory cytokines by Th1 CD4(+) T cells, contribution of V gamma 9/V delta 2 T lymphocytes to immune protection against this pathogen is suggested by the antimycobacterial reactivity of this subset and its ability to produce large amounts of Th1 cytokines. Here we show that V gamma 9/V delta 2 T lymphocytes kill macrophages harboring live M. tuberculosis. The cytotoxic activity of V gamma 9/V delta 2 T lymphocytes was not MHC class I or class II restricted but was blocked by anti-TCR monoclonal antibodies, thus indicating that it involved specific interaction between the TCR and the target cell. The cytotoxicity of V gamma 9/V delta 2 T lymphocytes was not mediated by TNF-alpha or Fas-Fas ligand, but was shown to occur through a granule-dependent mechanism that resulted in reduction of the viability of intracellular bacilli. Perforin was shown to play an important role in killing of both infected macrophages and intracellular mycobacteria. These data strongly suggest that V gamma 9/V delta 2 T lymphocytes contribute to the host defense against M. tuberculosis infection.