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CD4-CD8-???? and ???? T cells display inflammatory and regulatory potentials during human tuberculosis

By Melina de Barros Pinheiro, Lis Ribeiro do Valle Antonelli, Renato Sathler Avelar, Danielle Marquete Vitelli Avelar, Silvana Spindola de Miranda, T??nia Mara Pinto Dab??s Guimar??es, Andrea Teixeira Carvalho, Olindo Assis Martins Filho and Vicente de Paulo Coelho Peixoto de Toledo


T-cells play an important role controlling immunity against pathogens and therefore influence the outcome of human diseases. Although most T-lymphocytes co-express either CD4 or CD8, a smaller T-cell subset found the in the human peripheral blood that expresses the ???? or ???? T-cell-receptor (TCR) lacks the CD4 and CD8 co-receptors. These double negative (DN) T-cells have been shown to display important immunological functions in human diseases. To better understand the role of DN T-cells in human Mycobacterium tuberculosis, we have characterized their frequency, activation and cytokine profile in a well-defined group of tuberculosis patients, categorized as severe and non-severe based on their clinical status. Our data showed that whereas high frequency of ???? DN T-cells observed in M. tuberculosis-infected patients are associated with disease severity, decreased proportion of ???? DN T-cells are found in patients with severe tuberculosis. Together with activation of CD4+ and CD8+ T-cells, higher frequencies of both ???? and ???? DN T-cells from tuberculosis patients also express the chronic activation marker HLA-DR. However, the expression of CD69, an early activation marker, is selectively observed in DN T-cells. Interestingly, while ???? and ???? DN T-cells from patients with non-severe tuberculosis display a pro-inflammatory cytokine profile, characterized by enhanced IFN-??, the ???? DN T-cells from patients with severe disease express a modulatory profile exemplified by enhanced interleukin-10 production. Overall, our findings suggest that ???? and ???? DN T-cell present disparate immunoregulatory potentials and seems to contribute to the development/maintenance of distinct clinical aspects of TB, as part of the complex immunological network triggered by the TB infection

Topics: Mycobacterium tuberculosis, T-cells
Publisher: Public Library of Science one
Year: 2012
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