CD4+ CD25highforkhead box protein 3+ regulatory T lymphocytes suppress interferon-γ and CD107 expression in CD4+and CD8+ T cells from tuberculous pleural effusions

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 (T-reg) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of T-reg (CD4(+)CD25(high)forkhead box protein 3(+)), interferon (IFN)- 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 CD4(+)CD25(+), CD4(+)CD25(high)FoxP3(+) and CD8(+)CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+)CD25(low/neg)IL-10(+) in PB and CD4(+)CD25(low/neg)IFN-(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+)CD107(+) and CD8(+)CD107(+) cells was observed in PF. T-reg depletion enhanced the in-vitro M. tuberculosis-induced IFN- and CD4(+) and CD8(+) degranulation responses and decreased CD4(+)IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy T-reg cells effectively inhibit not only IFN- expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.