We have previously demonstrated that NK cells and CD1d-restricted NKT cells regulate clinical and pathological manifestations of experimental autoimmune encephalomyelitis(EAE), an animal model for multiple sclerosis(MS). It is important to address whether NK and NKT cells are also involved in the pathogenesis of human MS. Our laboratory has recently showed that NK cells as well as CD4+ NKT cells are biased for secreting type 2 cytokines in the remission phase of MS. However, CD4- CD8- NKT cells, that mainly secrete TNF-alpha and IFN-gamma, are reduced in number and attenuated in cytokine secretion. These results support our postulate that NK and NKT cells are involved in the regulation of MS.