Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis

作者：Avneesh Kumar Singh, Michael T. Wilson, Seokmann Hong, Danyvid Olivares–Villagómez, Caigan Du, Aleksandar K. Stanic, Sebastian Joyce, Subramaniam Sriram, Yasuhiko Koezuka, Luc Van Kaer · 发表于：The Journal of Experimental Medicine · 年份：2001 · DOI：10.1084/jem.194.12.1801 · 被引用次数：389 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、IL-33, ST2, and ILC Pathways

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.