Susceptibility of Mice Deficient in CD1D or TAP1 to Infection with Mycobacterium tuberculosis

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Abstract
Cellular immunity against Mycobacterium tuberculosis controls infection in the majority of infected humans. Studies in mice have delineated an important role for CD4+ T cells and cytokines including interferon γ and tumor necrosis factor α in the response to infection with mycobacteria. Recently, the identification of CD8+ CD1-restricted T cells that kill M. tuberculosis organisms via granulysin and the rapid death after infection of β2 microglobulin deficient mice in humans has drawn attention to a critical role for CD8+ T cells. The nature of mycobacterial-specific CD8+ T cells has 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 defense against tuberculosis as transporter associated with antigen processing (TAP)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 peptide antigen presentation and provides further evidence that class I MHC–restricted CD8+ T cells, the major T cell subset activated by this antigen processing pathway, play an essential role in immunity to tuberculosis.