? ? Tuberculosis remains one of the leading public health problems in the world today. HIV epidemic clearly is the most important risk factor. While human CD4 T cells play a crucial role in immune protection against M. tuberculosis infection, other T cell populations are not well characterized for their roles in immunity to tuberculosis. Phosphoantigen-specific V?2Vd2 T cells exist only in primates and constitute 60-95% of total human ?d T cell population in the blood. We have recently demonstrated that macaque V?2Vd2 T cells can mount adaptive immune responses during BCG and M. tuberculosis infections, and that the capacity of memory V?2Vd2 T cells to rapidly expand coincides with immunity to acutely fatal tuberculosis. We therefore hypothesize that V?2Vd2 T cells play a role in immunity to tuberculosis and AIDS-related reactivation tuberculosis. To test this hypothesis, we have adapted macaque models of pulmonary tuberculosis and AIDS-related tuberculosis-like disease. For this project, we will ? ? I. Determine if enhanced activation of V?2Vd2 T cells by phosphoantigen treatment during M. tuberculosis infection can attenuate disease course of tuberculosis in immune competent and SIV mac-infected macaques. ? ? II. Determine if restored V?2Vd2 T cell responses during antiretroviral therapy or combined antiretroviral-phosphoantigen treatment contribute to protection against SIV-related tuberculosis-like disease or SHIV-induced reactivation tuberculosis. ? ? III. Determine the utility of vaccination of V?2Vd2 T cells in delay or prevention of tuberculosis in immune competent and SHIV-infected monkeys. ? ?
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