Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell-mediated autoimmunity. V(alpha)14 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 V(alpha)14 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.
Singh
A K
AK
Department of Microbiology and Immunology, Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, TN 37232-0295, USA.
Wilson
M T
MT
Hong
S
S
Olivares-Villagómez
D
D
Du
C
C
Stanic
A K
AK
Joyce
S
S
Sriram
S
S
Koezuka
Y
Y
Van Kaer
L
L
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D015551:Autoimmunity; D003602:Cytotoxicity, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005699:Galactosylceramides / Q000276:immunology*; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology
D018949:Antigens, CD1; C419394:CD1b antigen; D005699:Galactosylceramides