Effects of anti-CD70 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease.

ABSTRACT

Ligation of CD27, a member of the tumor necrosis factor (TNF) receptor family, by its ligand CD70 is thought to be important in T cell activation, expansion and survival, B cell activation, and NK cell activation. We examined the role of CD70 in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) mice. Blocking of CD70 in effector phase by anti-CD70 monoclonal antibody (mAb) suppressed the development of TMEV-IDD. The number of IFN-gamma- or TNF-alpha-producing cells in the spleen and mRNA levels of IFN-gamma and TNF-alpha in spinal cord were decreased in mice treated with anti-CD70 mAb at the effector phase. In contrast, treatment with anti-CD70 mAb in induction phase failed to reduce these responses, compared to nonspecific IgG-treated control mice. These data suggest that CD70 is critically involved in the pathogenesis of TMEV-IDD and that antibodies against CD70 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis.