SUMMARY: Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4CD25forkhead box protein 3), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4CD25, CD4CD25FoxP3 and CD8CD25 cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4CD25IL-10 in PB and CD4CD25IFN-γ in PF; meanwhile, CD25 mainly expressed IL-10 in both compartments. A high proportion of CD4CD107 and CD8CD107 cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4 and CD8 degranulation responses and decreased CD4IL-10 cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4 and CD8 cells to degranulate in response to M. tuberculosis.