[Therapeutic strategy for multiple sclerosis targeting NK and NKT cells]

Recent works from our laboratory have demonstrated that natural killer (NK) cells and CD1d-restricted NKT cells are functionally biased toward producing type 2 cytokine in the remission phase of multiple sclerosis, an autoimmune disease putatively mediated by Th1 T cells. Indirect evidence would indicate that the type 2 bias of NK and NKT cells is not the cause of MS but an adaptive change to protect against activation of pathogenic Th1 cells. In fact, NK cells biased for producing IL-5 (NK2 cells) would inhibit induction of Th1 cells in vitro. Here I propose that it is a reasonable strategy for the control of MS to maximize and/or optimize the regulatory potentials of the innate regulatory cells. We have already found that experimental autoimmune encephalomyelitis (EAE), an animal model for MS, can be inhibited when NKT cells are partially stimulated by glycolipid ligands for NKT cells. Experiments proved that the suppression of disease is mediated by IL-4 produced by NKT cells. Future studies should be directed for identifying useful ligands for inducing regulatory cytokines from NK and NKT cells.