Th2 bias of CD4+ NKT cells derived from multiple sclerosis in remission

Abstract

Although CD1d-restricted NKT cells have been implicated as a participant in the regulatory mechanism of autoimmune diseases, it remains unclear how they would regulate human autoimmune diseases such as multiple sclerosis (MS). Furthermore, although the NKT cells comprise CD4+ and CD4- populations, prior studies have often represented them as simply a CD4- population. Given that CD4+ and CD4- NKT cells may represent functionally distinct populations, it appears crucial to examine the individual NKT subset in autoimmune diseases. Here we studied the frequency and cytokine phenotypes of the CD4+ and CD4- NKT cells in fresh peripheral blood mononuclear cells, and of α-galactosylceramide-stimulated short-term cell lines obtained during the remission or relapse phase of MS as compared with from healthy subjects (HS). Here we report that CD4+ NKT line cells expanded from MS in remission (MS-rem) would produce a larger amount of IL-4 than those from HS or from MS in relapse (MS-rel). They were significantly biased for Th2 as judged by the IL-4/IFN-γ balance. However, there was no functional bias toward Th1 or Th2 in CD4- NKT line cells from MS-rem due to the defects in both IFN-γ and IL-4 production, compared with HS. Of note, although double-negative NKT cells in the periphery were greatly reduced, the reduction of CD4+ NKT cells was only marginal, if any, in MS-rem compared with HS. The Th2 bias of CD4+ NKT line cells from MS-rem may support an immunoregulatory role for the CD4+ NKT cells in vivo.