Susceptibility of mice deficient in CD1D or TAP1 to infection with Mycobacterium tuberculosis

Cellular immunity against Mycobacter tuberculosis controls infection in the majority of infected humans. Studies in mace have delineated an important role for CD4(+) T cells and cytokines including interferon gamma and tumor necrosis factor cr in the response to infection with mycobacteria. Recently , the identification of CD8(+) CD1-restricted T cells that kill M. tubercul osis organisms via granulysin and the rapid death after infection of beta 2 microglobulin deficient mice in humans has drawn attention to a critical r ole for CD8+ T cells. The nature of mycobacterial-specific CD8(+) T cells h as been an enigma because few have been identified in any species. Here, we delineate the contribution of class I MHC-restricted T cells in the defens e against tuberculosis as transporter associated with antigen processing (T AP)1-deficient mice died rapidly, bore a greater bacterial burden, and had more severe tissue pathology than control mice. In contrast, CD1D(-/-) mice were not significantly different in their susceptibility to infection than control mice. This data demonstrates a critical role for TAP-dependent pep tide antigen presentation and provides further evidence that class I MHC-re stricted CD8+ T cells, the major T cell subset activated by this antigen pr ocessing pathway, play an essential role in immunity to tuberculosis.