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 C57BL/6 (B6) mice with the myelin oligodendrocyte glycoprotein (MOG)_35-55 peptide induces a mild form of monophasic EAE. When mice were deprived of NK cells by antibody treatment before immunization, they developed a more serious form of EAE associated with relapse. Aggravation of EAE by NK cell deletion was also seen in β2-microglobulin^−/− (β2m^−/−) mice, indicating that NK cells can play a regulatory role 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_35-55. EAE passively induced by the MOG_35-55-specific T cell line was also enhanced by NK cell deletion in B6, β2m^−/−, and recombination activation gene 2 (RAG-2)^−/− mice, indicating that the regulation 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 antigen or cytokine stimulation. Taken together, we conclude that NK cells are an important regulator for EAE in both induction and effector phases.