A critical role of cyclon, a novel cytokine-inducible gene, in the regulation of immune homeostasis (128.31)

Abstract

Autoimmunity, which results from hyperreactivity and hypersensitivity of lymphocytes against self antigens, can be caused by various defects in lymphoid cells, including impaired activation induced cell death (AICD) in effector T and B cells. Elimination of activated self-reactive T and B cells may effectively cure autoimmune diseases. We recently identify a novel cytokine-inducible gene, cyclon, by DNA microarray analysis. Cyclon is induced in both CD4+ and CD8+ T cells by T cell receptor ligation. Our data show that transgenic expression of Cyclon has no significant effect on T cell development and functions in wild-type mice. However, transgenic expression of Cyclon normalizes the number of activated T cells and suppresses enlargement of peripheral lymphoid organs in some autoimmune mice such as mice lacking the α subunit or the common γ chain of Interleukin-2 receptor. in vitro assays also suggest that the transgenic expression of Cyclon decreases viability of activated T cells and enhances AICD. Collectively, these results indicate that Cyclon may play an important role in immunosuppression by enhancing AICD. This work is supported by NIH grant R01 AI059315 to H. F.