Immune Response and Interaction of MAIT Cell and Vgamma2Vdelta2 T Cell Subsets in TB Infection of Primate

TB remains the main cause of mortality and morbidity worldwide. While accumulated studies confirmed that MAIT cells were related to TB infection, the immune response and effector function of MAIT cells in different tissue compartments remain poorly characterized in TB infection of humans. Here, we demonstrated that MAIT cells preferentially trafficked and accumulated to the pulmonary compartment from the peripheral blood in a nonhuman primate model of TB infection. These MR-1 restricted lung MAIT cells in the lung constitutively produced the pro-inflammatory cytokine mTNF-alpha. We further elucidated via Ab neutralization assay that MAIT cells directly isolated from TB-infected lung and other tissues could inhibit the intracellular growth of M.tuberculosis in a TNF-alpha/IFN-gamma dependent fashion. Surprisingly, we observed that the HMBPP-activated V gamma2Vdelta 2 T cells down-regulated the de novo production of mTNF-alpha by MAIT cells, and an Ab neutralizing assay indicated that the down-regulation induced by V gamma2Vdelta 2 T cells was IFN-gamma dependent. These novel findings of MAIT cells in early TB infections warrant further research on the function of MAIT cells, and their role in TB infection in humans.