REGULATION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY NATURAL-KILLER (NK) CELLS

In this report, we establish a regulatory role of natural killer (NK) cells in experimental autoimmune encephalomyelitis (EAE), a prototype T helper cell type 1 (Th1)-mediated disease. Active sensitization of C 57BL/6 (Bb) mice with the myelin oligodendrocyte glycoprotein (MOG)(35 -55) peptide induces a mild form of monophasic EAE. When mice were dep rived of NK cells by antibody treatment before immunization, they deve loped a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in beta 2-microglobulin(-/-) (beta 2m(-/-)) mice, indicating that NK cells can play a regulatory ro le in a manner independent of CD8(+) T cells or NK1.1(+) T cells (NK-T cells). The disease enhancement was associated with augmentation of T cell proliferation and production of Th1 cytokines in response to MOG (35-35). EAE passively induced by the MOG(35-55)-specific T cell Line was also enhanced by NK cell deletion in B6, beta 2m(-/-), and recombi nation activation gene 2 (RAG-2)(-/-) mice, indicating that the regula tion by NK cells can be independent of T, B, or NK-T cells. We further showed that NK cells inhibit T cell proliferation triggered by antige n or cytokine stimulation. Taken together, we conclude that NK cells a re an important regulator for EAE in both induction and effector phase s.