title: 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 alpha-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 T(h)2 as judged by the IL-4/IFN-gamma balance. However, there was no functional bias toward T(h)1 or T(h)2 in CD4(-) NKT line cells from MS-rem due to the defects in both IFN-gamma 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 T(h)2 bias of CD4(+) NKT line cells from MS-rem may support an immunoregulatory role for the CD4(+) NKT cells in vivo.
authors.affiliation: Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Araki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kondo
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005699:Galactosylceramides / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D009103:Multiple Sclerosis / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D005699:Galactosylceramides