Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis

Avneesh K. Singh, Michael T. Wilson, Seokmann Hong, Danyvid Olivares-Villagómez, Caigan Du, Aleksandar K. Stanic, Sebastian Joyce, Subramaniam Sriram, Yasuhiko Koezuka, Luc Van Kaer

Research output: Contribution to journalArticlepeer-review

349 Scopus citations


Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell-mediated autoimmunity. Vα14 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 Vα14 NKT cells by the glycosphingolipid α-galactosylceramide (α-GalCer) protects susceptible mice against EAE. β-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE. Furthermore, α-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 α-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. α-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 α-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.

Original languageEnglish (US)
Pages (from-to)1801-1811
Number of pages11
JournalJournal of Experimental Medicine
Issue number12
StatePublished - Dec 17 2001
Externally publishedYes


  • Autoimmunity
  • CD1d
  • Experimental autoimmune encephalomyelitis
  • Immunotherapy
  • NKT cells

ASJC Scopus subject areas

  • Medicine(all)


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