Int Immunol 2003 Feb;15(2):279-288
Araki M, Kondo T, Gumperz JE, Brenner MB, Miyake S, Yamamura T.
Department of Immunology, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, 1 Jimmy Fund Way, Boston MA 02115, USA.
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.