Engagement of toll-like receptor 2 on CD4 ⁺ T cells facilitates local immune responses in patients with tuberculous pleurisy

Background. Although it has been recognized that Mycobacterium tuberculosis contains large amounts of Tolllike receptor 2 (TLR2) ligands, their direct effects on CD4 ⁺ T cells and the clinical implications have not been determined. Methods. With the recent finding that activated CD4 ⁺ T cells express TLR2 as a costimulatory receptor, we hypothesized that M. tuberculosis and its components may directly affect CD4 ⁺ T cells by engaging TLR2, thus facilitating the expansion and function of these lymphocytes in tuberculous pleura. Results. Our results indicate that CD4 ⁺ T cells from the pleural fluid and peripheral blood of patients with tuberculosis show significantly increased TLR2 expression, compared with those from healthy donors. TLR2 ligand activity was also significantly higher in the tuberculous pleural fluid than in the serum from healthy donors or patients with pulmonary tuberculosis. M. tuberculosis TLR2 ligands, 19-kDa lipoprotein, and live bacillus CalmetteGuérin all modulated cytokine production (interferon 7 and interleukin 17), cellular proliferation, survival, and migration of CD4+ T cells isolated from pleural fluid and activated with anti-CD3 and anti-CD28. Conclusion. These data indicate that direct interaction between M. tuberculosis TLR2 ligands and CD4 ⁺ T cells facilitated local CD4 ⁺ T cell immune responses in patients with tuberculous pleurisy.