Costimulation-dependent modulation of experimental autoimmune encephalomyelitis by ligand stimulation of V alpha 14 NK T cells

J Immunol. 2001 Jan 1;166(1):662-8. doi: 10.4049/jimmunol.166.1.662.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a Th1 cell-mediated autoimmune disease that can be protected against by stimulating regulatory cells. Here we examined whether EAE can be purposefully modulated by stimulating Valpha14 NK T cells with the CD1d-restricted ligand alpha-galactosylceramide (alpha-GC). EAE induced in wild-type C57BL/6 (B6) mice was not appreciably altered by injection of alpha-GC. However, EAE induced in IL-4 knockout mice and IFN-gamma knockout mice was enhanced or suppressed by alpha-GC, respectively. This indicates that the IL-4 and IFN-gamma triggered by alpha-GC may play an inhibitory or enhancing role in the regulation of EAE. We next studied whether NK T cells of wild-type mice may switch their Th0-like phenotype toward Th1 or Th2. Notably, in the presence of blocking B7.2 (CD86) mAb, alpha-GC stimulation could bias the cytokine profile of NK T cells toward Th2, whereas presentation of alpha-GC by CD40-activated APC induced a Th1 shift of NK T cells. Furthermore, transfer of the alpha-GC-pulsed APC preparations suppressed or enhanced EAE according to their ability to polarize NK T cells toward Th2 or Th1 in vitro. These results have important implications for understanding the role of NK T cells in autoimmunity and for designing a therapeutic strategy targeting NK T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / immunology
  • B7-2 Antigen
  • CD40 Antigens / pharmacology
  • Encephalomyelitis, Autoimmune, Experimental / etiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Epitopes, T-Lymphocyte / immunology
  • Galactosylceramides / administration & dosage
  • Galactosylceramides / metabolism
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Isotypes / biosynthesis
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Ligands
  • Lymphocyte Activation* / drug effects
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / administration & dosage
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Oligodendroglia / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Vaccination

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • B7-2 Antigen
  • CD40 Antigens
  • Cd86 protein, mouse
  • Epitopes, T-Lymphocyte
  • Galactosylceramides
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Ligands
  • Membrane Glycoproteins
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Antigen, T-Cell, alpha-beta