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

摘要

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 (CD4⁺CD25^highforkhead 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 CD4⁺CD25⁺, CD4⁺CD25^highFoxP3⁺ and CD8⁺CD25⁺ cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4⁺CD25^lowegIL-10⁺ in PB and CD4⁺CD25^lowegIFN-γ⁺ 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. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4⁺ and CD8⁺ degranulation responses and decreased CD4⁺IL-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.