J Exp Med 2001 Dec 17;194(12):1801-1811
Singh AK, Wilson MT, Hong S, Olivares-Villagomez D, Du C, Stanic AK, Joyce S, Sriram S, Koezuka Y, Van Kaer L.
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232. Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, TN 37232. Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232. Pharmaceutical Research Laboratory, Kirin Brewery Company Limited, Takasaki-shi, Gunma 370-12, Japan.
Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell-mediated autoimmunity.
Valpha14 natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I-like protein CD1d.
Here, we show that activation of Valpha14 NKT cells by the glycosphingolipid alpha-galactosylceramide (alpha-GalCer) protects susceptible mice against EAE.
beta-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE.
Furthermore, alpha-GalCer was unable to protect CD1d knockout (KO) mice against EAE, indicating the requirement for an intact CD1d antigen presentation pathway.
Protection of disease conferred by alpha-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. alpha-GalCer was unable to protect IL-4 KO and IL-10 KO mice against EAE, indicating a critical role for both of these cytokines.
Because recognition of alpha-GalCer
by NKT cells is phylogenetically conserved, our findings have identified
NKT cells as novel target cells for treatment of inflammatory diseases
of the central nervous system.
PMID: 11748281 [PubMed - as supplied
PMID: 11748281 [PubMed - as supplied by publisher]