Abstract
Newly discovered IL-9–producing CD4+ helper T cells (Th9 cells) have been reported to contribute to tissue inflammation and immune responses, however, differentiation and immune regulation of Th9 cells in tuberculosis remain unknown. In the present study, our data showed that increased Th9 cells with the phenotype of effector memory cells were found to be in tuberculous pleural effusion as compared with blood. TGF-β was essential for Th9 cell differentiation from naïve CD4+ T cells stimulated with PMA and ionomycin in vitro for 5 h, and addition of IL-1β, IL-4 or IL-6 further augmented Th9 cell differentiation. Tuberculous pleural effusion and supernatants of cultured pleural mesothelial cells were chemotactic for Th9 cells, and this activity was partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell repairing and inhibited IFN-γ-induced pleural mesothelial cell apoptosis. Moreover, pleural mesothelial cells promoted Th9 cell differentiation by presenting antigen. Collectively, these data provide new information concerning Th9 cells, in particular the collaborative immune regulation between Th9 cells and pleural mesothelial cells in human M. tuberculosis infection. In particular, pleural mesothelial cells were able to function as antigen-presenting cells to stimulate Th9 cell differentiation.
Highlights
Tuberculosis presents a challenging worldwide public heath problem
We have demonstrated that Th9 cells were present in Tuberculous pleural effusion (TPE), and the numbers of Th9 cells represented in TPE were much higher than those in the corresponding blood
Studies in mice have shown that TGF-b derived Th2 cells to lose their characteristic profile and switched to Th9 cells or, in combination with IL-4, promoted the differentiation of Th9 cells directly [11], and that IL-4 blocked the generation of TGF-b-induced Tregs and instead induced the development of Th9 cells that could produced IL-10 [12]
Summary
According to the World Health Organization, one third of the world’s population are thought to be infected with M. tuberculosis, but only 10% of the infected individuals would develop active tuberculosis [1]. Most infected individuals will stay healthy throughout their lifetime and develop a latent infection with no sign of disease. They can be regarded as being protected against the disease by the immune response induced through natural infection. Infection with M. tuberculosis elicits humoral and cellular immune responses, and T cell-mediated immunity, comprising CD4+ and CD8+ cells, is thought to be important for effective prevention of disease after M. tuberculosis infection [2]. M. tuberculosis are seldom eradicated, and a few M. tuberculosis can persist for years, residing inside macrophages in granulomas and evading elimination by the host immune response [3]
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