O036 IL-17-producing gamma-delta T cells are crucial for the development of autoimmune arthritis in IL-1 receptor antagonist-deficient mice

作     者：A. Akitsu H. Ishigame S. Kakuta S. Saijo Y. Iwakura 

作者机构：The Institute of Medical Science University of Tokyo Japan Japan Society for the Promotion of Science Japan Core Research for Evolutional Science and Technology Japan Science and Technology Agency Tokyo Japan Division of Laboratory Animal Research Institute for Bio Medical Sciences Tokyo University of Science Chiba Japan 

出 版 物：《Cytokine》 

年 卷 期：2012年第59卷第3期

页      面：514-514页

学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

摘      要：Introduction A high proportion of IL-17-producing gamma-delta T (gd17) cells was detected in joints of Il1rn −/− mice, a model of rheumatoid arthritis, whose development depends on IL-17 and T cells. However, their pathogenic roles are not well understood. Methods We assessed the effect of gdT cell or CD4 + T cell depletion in Il1rn −/− mice using a monoclonal antibodies. Then, we examined the pathogenic activity of gd17 cells by adoptive transfer. Results To clarify the roles of gdT cells and CD4 + T cells in the development of arthritis, gdT cells or CD4 + T cells were depleted in Il1rn −/− miceusing antibodies. The development of disease was suppressed in both cases, suggesting both gdT cells and CD4 + T cells were involved in the pathogenesis. Then, the pathogenic role of gd17 cells in the absence of Th17 cells was examined. We generated mice with gd17 cells, but without Th17 cells, by adoptively transferring Il17 −/− Il1rn −/− -CD4 + T cells into nu/nu mice in which gd17 cells are present. We found that these mice still developed arthritis and that only gdT cells produced IL-17. To corroborate that the development of arthritis in this transfer system is dependent on IL-17, we adoptively transferred Il17 −/− Il1rn −/− -CD4 + T cells into Il17 −/− - nu/nu mice. The development of arthritis was significantly suppressed in Il17 −/− - nu/nu mice transferred with Il17 −/− Il1rn −/− -CD4 + T cells compared with Il17 +/+ - nu/nu mice transferred with Il17 −/− Il1rn −/− -CD4 + T cells, suggesting that extrathymic gd17 cells are also important for the development of arthritis. Interestingly, Il1rn −/− mice on the nu/nu mice background, in which only gd17 cells but not thymus-derived T cells are present, also developed arthritis. Thus, gd17 cells alone can induce arthritis without involvement of CD4 + T cells only in Il1rn −/− background mice in which excess IL-1 signaling is introduced. In contrast, a combination of CD4 + T cells and gd17 cells was required for the devel