Engagement of Toll-Like Receptor 2 on CD4+ T Cells Facilitates Local Immune Responses in Patients with Tuberculous Pleurisy

• Published in: The Journal of infectious diseases Vol. 200; no. 3; pp. 399 - 408
• Main Authors: Chen, Xinchun, Zhang, Mingxia, Zhu, Xiuyun, Deng, Qunyi, Liu, Haiying, Larmonier, Nicolas, Graner, Michael W., Zhou, Boping
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.08.2009; University of Chicago Press; Oxford University Press
• Subjects: Adult; Bacteria; Bacterial diseases; Biological and medical sciences; Case-Control Studies; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Movement; Cells, Cultured; Cytometry; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - immunology; Human bacterial diseases; Humans; Infections; Infectious diseases; Interleukin-8 - metabolism; Ligands; Lipoproteins; Male; Medical sciences; Microbiology; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - metabolism; Pleural tuberculosis; Pleurisy; Pulmonary tuberculosis; T lymphocytes; Toll like receptors; Toll-Like Receptor 2 - immunology; Toll-Like Receptor 2 - metabolism; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pleural - immunology; Tuberculosis, Pulmonary - immunology; Young Adult; Human; Infection; Tuberculosis; Microbiology; Respiratory disease; Toll like receptor 2; Pleurisy; Bacteriosis; Pleural disease; Cellular immunity; Mycobacterial infection
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/600075

Background 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. 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 Calmette-Guérin all modulated cytokine production (interferon γ 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.