%0 Journal Article %T CD4-CD8-¦Á¦Â and ¦Ã¦Ä T Cells Display Inflammatory and Regulatory Potentials during Human Tuberculosis %A Melina B. Pinheiro %A Lis R. Antonelli %A Renato Sathler-Avelar %A Danielle M. Vitelli-Avelar %A Silvana Spindola-de-Miranda %A Tania M. P. D. Guimar£¿es %A Andrea Teixeira-Carvalho %A Olindo A. Martins-Filho %A Vicente P. C. P. Toledo %J PLOS ONE %D 2012 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0050923 %X 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 ¦Á¦Â or ¦Ã¦Ä 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 ¦Á¦Â DN T-cells observed in M. tuberculosis-infected patients are associated with disease severity, decreased proportion of ¦Ã¦Ä DN T-cells are found in patients with severe tuberculosis. Together with activation of CD4+ and CD8+ T-cells, higher frequencies of both ¦Á¦Â and ¦Ã¦Ä 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 ¦Á¦Â and ¦Ã¦Ä DN T-cells from patients with non-severe tuberculosis display a pro-inflammatory cytokine profile, characterized by enhanced IFN-¦Ã, the ¦Ã¦Ä DN T-cells from patients with severe disease express a modulatory profile exemplified by enhanced interleukin-10 production. Overall, our findings suggest that ¦Á¦Â and ¦Ã¦Ä 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0050923