Culosis vaccine candidates, the improvement of tuberculosis diagnostics or the development of more effective and shorter treatment regimens [23]. Furthermore, host biomarkers in tuberculosis are needed to provide correlates of risk, protection, and response to therapy. In the present study, ab and cd DN T-cells from infected MedChemExpress Tunicamycin patients expressed increased levels not only of CD69 but also higher frequencies of HLA-DR 
expressing cells ex vivo, which are indicators of recent antigenic exposure. Increased expression of HLA-DR in patients with TB was reported before, but no correlation with clinical outcome 22948146 was done [24]. The expression of either CD69 or HLA-DR on ab 12926553 DN T-cells of infected patients is similarly increased in TB patients presenting the non-severe and severe form of the disease. cd DN T-cells from TB patients also display an activated phenotype compared with healthy donors. Thus, overall, the DN T population from TB-infected patients presented a profile compatible with previous antigen exposure (HLA-DR) and recent activation (CD69). Host effector immune response against M. tuberculosis is related to the presence of a strong Th1 response and memory, leading to the production of immune mediators that activate parasiteinfected macrophages for 
parasite destruction. One critical cytokine for host control of M. tuberculosis is IFN-c. IFN-c is required for induction of NO synthase type 2 and other effector molecules in infected macrophages. Both CD4+ and CD8+ T-cells and NK cells have been shown to be sources of this protective cytokine in M. tuberculosis infection [13,16]. The essential role of IFN-c is evident from the increased risk of tuberculosis in: (i) individuals with deficiency of IFN-c and interleukin-12, which promotes Th1 cell differentiation; (ii) animal models Bromopyruvic acid depleted of CD4+ T-cell during the experimental infection; (iii) HIV-infected individuals [25,26]. ab DN T-cells from TB-patients displayed a higher commitment to the production of IFN-c. Moreover they also contained a higher proportion of IFN-c producing cells than the CD4+ and CD8+ ab T-cell population. High frequencies of IFN-c producing cells in TB group are accounted by patients presenting the non-severe form of tuberculosis. A great proportion of ab DN T-cells from nsTB patients are maintain the ability of IFN-c production, which is lost for sTB patients. The reduction of TB-specific T-cells and the impairment of Th1 immune responseRole of CD4-CD8-ab and cd T Cells in TuberculosisFigure 3. Higher frequencies of IFN-c producing DN ab T-cells are found in nsTB patients. Representative contour plots showing the proportions of IFN-c producing CD4 (left panel), CD8 (middle panel) and DN (right panel) ab-T cells (A). The percentages of IFN-c (B), TNF-a (C) and IL10 (D) expression within CD4+ (left panels), CD8+ (middle panels) and DN (right panels) ab T-cells in healthy donors (HD, open symbols), TB (total TB, black symbols), nsTB (non-severe TB, light gray symbols) and sTB patients (severe TB, dark gray) were measured before treatment. PBMCs were stimulated with (MTB-Ag) for 48 hours. The boxes represent the means. doi:10.1371/journal.pone.0050923.gRole of CD4-CD8-ab and cd T Cells in TuberculosisFigure 4. DN cd T-cells from nsTB patients produce inflammatory cytokines whereas those from sTB produce more IL-10. Representative contour plots showing the proportions of IFN-c producing CD4 (left panel), CD8 (middle panel) and DN (right panel) cd-T cells (A). Percentages.Culosis vaccine candidates, the improvement of tuberculosis diagnostics or the development of more effective and shorter treatment regimens [23]. Furthermore, host biomarkers in tuberculosis are needed to provide correlates of risk, protection, and response to therapy. In the present study, ab and cd DN T-cells from infected patients expressed increased levels not only of CD69 but also higher frequencies of HLA-DR expressing cells ex vivo, which are indicators of recent antigenic exposure. Increased expression of HLA-DR in patients with TB was reported before, but no correlation with clinical outcome 22948146 was done [24]. The expression of either CD69 or HLA-DR on ab 12926553 DN T-cells of infected patients is similarly increased in TB patients presenting the non-severe and severe form of the disease. cd DN T-cells from TB patients also display an activated phenotype compared with healthy donors. Thus, overall, the DN T population from TB-infected patients presented a profile compatible with previous antigen exposure (HLA-DR) and recent activation (CD69). Host effector immune response against M. tuberculosis is related to the presence of a strong Th1 response and memory, leading to the production of immune mediators that activate parasiteinfected macrophages for parasite destruction. One critical cytokine for host control of M. tuberculosis is IFN-c. IFN-c is required for induction of NO synthase type 2 and other effector molecules in infected macrophages. Both CD4+ and CD8+ T-cells and NK cells have been shown to be sources of this protective cytokine in M. tuberculosis infection [13,16]. The essential role of IFN-c is evident from the increased risk of tuberculosis in: (i) individuals with deficiency of IFN-c and interleukin-12, which promotes Th1 cell differentiation; (ii) animal models depleted of CD4+ T-cell during the experimental infection; (iii) HIV-infected individuals [25,26]. ab DN T-cells from TB-patients displayed a higher commitment to the production of IFN-c. Moreover they also contained a higher proportion of IFN-c producing cells than the CD4+ and CD8+ ab T-cell population. High frequencies of IFN-c producing cells in TB group are accounted by patients presenting the non-severe form of tuberculosis. A great proportion of ab DN T-cells from nsTB patients are maintain the ability of IFN-c production, which is lost for sTB patients. The reduction of TB-specific T-cells and the impairment of Th1 immune responseRole of CD4-CD8-ab and cd T Cells in TuberculosisFigure 3. Higher frequencies of IFN-c producing DN ab T-cells are found in nsTB patients. Representative contour plots showing the proportions of IFN-c producing CD4 (left panel), CD8 (middle panel) and DN (right panel) ab-T cells (A). The percentages of IFN-c (B), TNF-a (C) and IL10 (D) expression within CD4+ (left panels), CD8+ (middle panels) and DN (right panels) ab T-cells in healthy donors (HD, open symbols), TB (total TB, black symbols), nsTB (non-severe TB, light gray symbols) and sTB patients (severe TB, dark gray) were measured before treatment. PBMCs were stimulated with (MTB-Ag) for 48 hours. The boxes represent the means. doi:10.1371/journal.pone.0050923.gRole of CD4-CD8-ab and cd T Cells in TuberculosisFigure 4. DN cd T-cells from nsTB patients produce inflammatory cytokines whereas those from sTB produce more IL-10. Representative contour plots showing the proportions of IFN-c producing CD4 (left panel), CD8 (middle panel) and DN (right panel) cd-T cells (A). Percentages.