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

An effective immune response against the intracellular pathogen Mycobacteri um tuberculosis is strictly dependent on T cell activation. Although this p rotective response mainly depends on local release of pro-inflammatory cyto kines by Th1 CD4(+) T cells, contribution of V gamma 9/V delta 2 T lymphocy tes to immune protection against this pathogen is suggested by the antimyco bacterial reactivity of this subset and its ability to produce large amount s of Th1 cytokines. Here we show that V gamma 9/V delta 2 T lymphocytes kil l macrophages harboring live M. tuberculosis. The cytotoxic activity of V g amma 9/V delta 2 T lymphocytes was not MHC class I or class II restricted b ut was blocked by anti-TCR monoclonal antibodies, thus indicating that it i nvolved specific interaction between the TCR and the target cell. The cytot oxicity 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 mecha nism that resulted in reduction of the viability of intracellular bacilli. Perforin was shown to play an important role in killing of both infected ma crophages 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.