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.