Involvement of CD70-CD27 interactions in the induction of experimental autoimmune encephalomyelitis.

CD70/CD27 are cell surface molecules belonging to the TNF/TNF-receptor families. Ligation of CD27 by its ligand CD70 is thought to be important in T cell activation and T cell-B cell interaction. However, the in vivo function of these molecules during the establishment of cell-mediated immunity remains unclear. In this study, we examined the contribution of CD70-CD27 interactions to cell-mediated immunity by investigating the effect of anti-CD70 mAb on the development of experimental autoimmune encephalomyelitis (EAE). Treatment of SJL/J mice with anti-CD70 mAb prevented EAE induced by immunization with PLP(139-151). The preventive effect of anti-CD70 mAb was not due to the inhibition of T cell priming and antibody production from B cells, or immune deviation. However, TNF-alpha production was suppressed by treatment with anti-CD70 mAb, indicating that the ameliorating effect of anti-CD70 mAb appeared, at least in part, to be mediated by the inhibition of TNF-alpha production. These results indicate that the CD70-CD27 interaction plays a pivotal role in the development of cell-mediated autoimmune disease.