5, 0.7 and 1.1 with MT-CW, whole-cell M. tuberculosis and whole-cell M. bovis BCG, respectively. In response to peptide pools of various RDs, mainly IFN- γ was secreted by PBMCs in the presence of peptide pools of RD1, RD5, RD7 and RD9 and RD10 (Fig. 6b), with IFN-γ:IL-10 ratios of 33, 8.6, 8.3, 6.5 and 4.8,

respectively, suggesting a Th1 bias. In contrast, mainly IL-10 was secreted in the presence of peptide pools of RD12, RD13 and RD15 (Fig. 6d), with IFN-γ:IL-10 ratios of 0.6, 0.6 and 0.4, respectively, suggesting a Th2 bias. However, both IFN-γ and IL-10 were secreted in the presence of peptide pools of RD4 and RD6 (Fig. 6b,d), with IFN-γ:IL-10 ratios of 1.9 and 1.1, respectively, which suggests no bias towards Th1 or Th2 cytokines. In the present study, human cellular immune responses were buy 3-deazaneplanocin A investigated by assessing Cetuximab price secretion of innate immune response-related pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β), and adaptive immune response related Th1 (IFN-γ, IL-2, TNF-β) and Th2 (IL-10, IL-4, IL-5) cytokines by PBMCs from pulmonary TB patients. The study of cellular immune responses and the definition of target molecules are important for the understanding of protective and pathogenic immune mechanisms in TB, and for identification of antigens suitable for diagnosis, and development of new vaccines (36–40). We found that the percentage of TB patient’s PBMCs

secreting detectable concentrations of various cytokines

and the absolute concentrations of different cytokines varied. However, secretion of proinflammatory cytokines was more marked as 88 to 100% patients did secrete these cytokines (Fig. 1a). These results confirm previous findings indicating spontaneous expression of messages governing, and secretion of, pro-inflammatory and chemotactic cytokines by PBMCs of TB patients (41–45). Furthermore, as compared to healthy subjects, TB patients secrete increased quantities of pro-inflammatory and chemotactic cytokines (41, 45). These chemotactic molecules assure recruitment of appropriate cells at the appropriate time to sites of disease activity. Thus secretion of multiple chemokines may be required to maintain granulomas by preventing cell movement out of them (46). The spontaneous secretion ioxilan by PBMCs of one or more Th1 and Th2 cytokines observed in this study indicates a mixed state of Th1/Th2 phenotype of cells with a shift towards Th2 cytokines. These results are compatible with previous findings reporting dominance of Th2 cytokines in TB patients, as compared to healthy controls (47, 48). Th2 dominance may play a role in the pathogenesis of the disease, as suggested previously (49). Complex mycobacterial antigens induced secretion of proinflammatory cytokines IL1-β, TNF-α and IL-6 but not IL-8, whereas RD peptides induced secretion of IL-6, only (Figs 2 and 3).