Regulatory T cell frequency and modulation of IFN-gamma and IL-17 in active and latent tuberculosis

Regulatory T cells (Tregs) play an essential role in immune homeostasis. In infectious diseases Tregs may inhibit protective responses facilitating pathogen multiplication and dissemination, but they may also limit the inflammatory response diminishing tissue damage. Although there is experimental and clinical evidence that Tregs are induced during Mycobacterium tuberculosis infection, their role in the immunopathogenesis of tuberculosis is still not completely understood. In this study, the phenotype, frequency and activity of circulating Tregs in active and latent tuberculosis were evaluated. Phenotypic analysis showed that Tregs were CD4(+)CD25(high)FOXP3(+)CD45RO(+)CD127(-). High levels of circulating Tregs were found in patients with active pulmonary tuberculosis, compared to individuals with latent infection. Treg activity was evaluated by ELISPOT by determining the effect of CD25(+) cell depletion on the frequency of IFN-gamma and IL-17 producing cells after in vitro stimulation with ESAT-6, CFP-10 and PPD. Treg depletion increased the frequency of IFN-gamma producing cells, without affecting the frequency of IL-17 producing cells, in both active and latent tuberculosis, irrespective of the antigen used. Neutralization of IL-10 did not have any effect on the frequency of IFN-gamma and IL-17 producing cells. Altogether, these results suggest that during active tuberculosis Tregs inhibit protective Th1 responses, but not the proinflammatory Th17 responses, facilitating mycobacterial replication and tissue damage.