IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis

J Immunol. 1996 Oct 15;157(8):3223-7.

Abstract

129/Sv mice are resistant to induction of experimental autoimmune encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice of this strain lacking the gene coding for the ligand-binding chain of the IFN-gamma receptor develop EAE with high morbidity and mortality. Spleen cells from sensitized IFN-gammaR-/- mice proliferated extensively when stimulated with MOG peptide in culture and produced high levels of IFN-gamma and TNF but no detectable IL-4. Transfer of spleen cells from sensitized IFN-gammaR-/- mice produced EAE in both IFN-gammaR+/+ and IFN-gammaR-/- recipients. Disease was severe in IFN-gammaR-/- recipients and mortality high (77%). Surviving mice remained moribund until termination of the experiments. IFN-gammaR+/+ recipients developed disease of equal severity, but with no mortality, and recovered significantly. These results indicate that IFN-gamma is not essential for the generation or function of anti-MOG35-55 effector cells but does play an important role in down-regulating EAE at both the effector and induction phase of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Surface
  • Autoantibodies / biosynthesis
  • Cytokines / biosynthesis
  • Down-Regulation
  • Encephalomyelitis, Autoimmune, Experimental / etiology*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Interferon gamma Receptor
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / immunology*
  • Myelin-Oligodendrocyte Glycoprotein
  • Oligodendroglia / immunology
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Spinal Cord / pathology
  • Spleen / immunology

Substances

  • Antigens, CD
  • Antigens, Surface
  • Autoantibodies
  • Cytokines
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Interferon
  • Interferon-gamma