The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 17 December 2001. doi:10.1084/jem.194.12.1801
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 119K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singh, A. K.
Right arrow Articles by Van Kaer, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singh, A. K.
Right arrow Articles by Van Kaer, L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2001/12/1801/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 12, December 17, 2001 1801-1811

Original Article

Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis

Avneesh K. Singh1,2, Michael T. Wilson1,2, Seokmann Hong1,2, Danyvid Olivares-Villagómez1,2, Caigan Du1,3, Aleksandar K. Stanic1, Sebastian Joyce1, Subramaniam Sriram1,3, Yasuhiko Koezuka4 and Luc Van Kaer1,2

1 Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
2 Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, TN 37232
3 Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37232
4 Pharmaceutical Research Laboratory, Kirin Brewery Company Limited, Takasaki-shi, Gunma 370-12, Japan

Address correspondence to Luc Van Kaer, Department of Microbiology and Immunology and Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Rm. 811 Light Hall, Nashville, TN 37232-0295. Phone: 615-343-2707; Fax: 615-343-2972; E-mail: vankael{at}ctrvax.vanderbilt.edu

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. ß-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.

Key Words: CD1d • NKT cells • experimental autoimmune encephalomyelitis • autoimmunity • immunotherapy


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS