Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis

Avneesh 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 journalArticle

Abstract

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
Volume194
Issue number12
DOIs
StatePublished - Dec 17 2001
Externally publishedYes

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Natural Killer T-Cells
Autoimmune Experimental Encephalomyelitis
Myelin Sheath
Antigens
Knockout Mice
CD1d Antigen
Galactosylceramides
T-Lymphocytes
Glycosphingolipids
Th2 Cells
Central Nervous System Diseases
Glycolipids
Antigen Presentation
T-Lymphocyte Subsets
Major Histocompatibility Complex
Autoimmunity
Interleukin-4
Interleukin-10
Cytokines
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Singh, A., Wilson, M. T., Hong, S., Olivares-Villagómez, D., Du, C., Stanic, A. K., ... Van Kaer, L. (2001). Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. Journal of Experimental Medicine, 194(12), 1801-1811. https://doi.org/10.1084/jem.194.12.1801

Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. / Singh, Avneesh; Wilson, Michael T.; Hong, Seokmann; Olivares-Villagómez, Danyvid; Du, Caigan; Stanic, Aleksandar K.; Joyce, Sebastian; Sriram, Subramaniam; Koezuka, Yasuhiko; Van Kaer, Luc.

In: Journal of Experimental Medicine, Vol. 194, No. 12, 17.12.2001, p. 1801-1811.

Research output: Contribution to journalArticle

Singh, A, Wilson, MT, Hong, S, Olivares-Villagómez, D, Du, C, Stanic, AK, Joyce, S, Sriram, S, Koezuka, Y & Van Kaer, L 2001, 'Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis', Journal of Experimental Medicine, vol. 194, no. 12, pp. 1801-1811. https://doi.org/10.1084/jem.194.12.1801
Singh, Avneesh ; Wilson, Michael T. ; Hong, Seokmann ; Olivares-Villagómez, Danyvid ; Du, Caigan ; Stanic, Aleksandar K. ; Joyce, Sebastian ; Sriram, Subramaniam ; Koezuka, Yasuhiko ; Van Kaer, Luc. / Natural killer T cell activation protects mice against experimental autoimmune encephalomyelitis. In: Journal of Experimental Medicine. 2001 ; Vol. 194, No. 12. pp. 1801-1811.
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