Interplay of Th1 and Th17 Cells in Murine Models of Malignant Pleural Effusion

Rationale: IFN-gamma-producing CD4(+) T (Th1) cells and IL-17-producing CD4(+) T (Th17) cells have been found to be involved in multiple malignancies; however, the reciprocal relationship between Th1 and Th17 cells in malignant pleural effusion (MPE) remains to be elucidated. Objectives: To explore the differentiation and immune regulation of Th1 and Th17 cells in the development of MPE in murine models. Methods: The distribution and differentiation of Th1 and Th17 cells in MPE were investigated in IFN-gamma(-/-), IL-17(-/-) and wild-type mice. The effects of Th1 and Th17 cells on the development of MPE and the survival of mice bearing MPE were also investigated. Measurements and Main Results: We have demonstrated that increased Th1 and Th17 cells could be found in MPE as compared with blood and spleen. Compared with wild-type mice, Th17 cells were markedly augmented in MPE from IFN-gamma(-/-)mice, and improved survival could be seen in IFN-gamma(-/-) mice. Th1 cell numbers were elevated in MPE from IL-17(-/-) mice, and decreased survival could be seen in IL-17(-/-) mice. The in vitro experiments showed that IFN-gamma deficiency promoted Th17-cell differentiation by suppressing the STAT3 pathway and that IL-17 deficiency promoted Th1-cell differentiation by suppressing the STAT1 pathway. Conclusions: In mouse models of MPE, IFN-gamma inhibited Th17-cell differentiation, whereas IL-17 inhibited Thl-cell differentiation. IL-17 inhibited the formation of MPE and improved the survival of mice bearing MPE; in contrast, IFN-gamma promoted MPE formation and mouse death..