Chen Xinchun, Zhang Mingxia, Zhu Xiuyun, Deng Qunyi, Liu Haiying, Larmonier Nicolas, Graner Michael W, Zhou Boping
Shenzhen Clinical Research Center for Infectious Diseases, Shenzhen Third Hospital, Shenzhen, China.
J Infect Dis. 2009 Aug 1;200(3):399-408. doi: 10.1086/600075.
Although it has been recognized that Mycobacterium tuberculosis contains large amounts of Toll-like receptor 2 (TLR2) ligands, their direct effects on CD4(+) T cells and the clinical implications have not been determined.
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.
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 Calmette-Guérin all modulated cytokine production (interferon gamma and interleukin 17), cellular proliferation, survival, and migration of CD4(+) T cells isolated from pleural fluid and activated with anti-CD3 and anti-CD28.
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.
尽管已经认识到结核分枝杆菌含有大量的Toll样受体2（TLR2）配体，但其对CD4(+) T细胞的直接作用及临床意义尚未明确。
鉴于最近发现活化的CD4(+) T细胞表达TLR2作为共刺激受体，我们推测结核分枝杆菌及其成分可能通过与TLR2结合直接影响CD4(+) T细胞，从而促进这些淋巴细胞在结核性胸膜炎中的扩增和功能。
我们的结果表明，与健康供体相比，结核病患者胸腔积液和外周血中的CD4(+) T细胞TLR2表达显著增加。结核性胸腔积液中的TLR2配体活性也显著高于健康供体或肺结核患者的血清。结核分枝杆菌TLR2配体、19 kDa脂蛋白和活卡介苗均能调节从胸腔积液中分离并用抗CD3和抗CD28激活的CD4(+) T细胞的细胞因子产生（干扰素γ和白细胞介素17）、细胞增殖、存活和迁移。
这些数据表明，结核分枝杆菌TLR2配体与CD4(+) T细胞之间的直接相互作用促进了结核性胸膜炎患者局部CD4(+) T细胞免疫反应。
