HIV-1 compromises CD8+T cell effector function in Mtb- infected lung

Tuberculosis (TB) remains a global health problem with more than 8 million new cases and 1 million deaths per year worldwide. HIV-1 infected persons have a greatly increased risk of Mycobacterium tuberculosis (M. tb) co-infection. A key feature of M.tb infection is the formation of granulomas, cellular accumulations composed of macrophages, epithelial cells, and a surrounding mantle of T cells, which are important for the containment of infection. The cytolytic T cell effector molecules, perforin and granulysin, play a critical role in protective immunity to M.tb. It has been shown that decreased expression of perforin and granulysin at the site of pulmonary disease is linked to chronic TB. However, the effects of HIV-1 on CD8+T cells numbers and expression of cytolytic effector molecules such as perforin and granulysin in M. tb induced granulomas has not been explored. In this study, we used immunohistological techniques to assess the differences in T cell populations, granulysin expression, and pathology in tissue sections from Mtb- and Mtb/HIV-1-infected human lung. Our results indicate that granulomas from persons with TB/HIV-1 are characterized by dysregulated T cell organization and poor expression of granulysin. We propose that defective granulysin expression by M.tb-specific CD8+T cells contributes to the development of disease in TB/HIV-1 co-infected persons.