Epitope spread is not critical for the relapse and progression of MOG 8-21 induced EAE in Biozzi ABH mice

J Neuroimmunol. 2005 Jul;164(1-2):76-84. doi: 10.1016/j.jneuroim.2005.04.006.

Abstract

Emerging autoimmunity (epitope-spreading) generated as a consequence of myelin damage is suggested to underlie the relapses in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG 8-21) induces relapsing EAE in ABH mice characterized by broadening of the autoimmune reportoire. Despite epitope spreading tolerance to the priming antigen, but not emerging epitope reactivities, resulted in long-term inhibition of clinical relapse. In contrast, spinal cord homogenate induced EAE was dominated by a proteolipid protein (PLP 56-70) autoreactivity despite the plethora of CNS antigens in the immunogen. This data suggests that during relapsing-remitting demyelinating disease the pathogenic process is dominated by the initiating antigen, with only a minor role played by emerging T-cell populations. These findings may have important implications for the efficacy of antigen-based immune therapies in autoimmune disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoproteins / toxicity
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes / immunology*
  • Epitopes / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Biozzi
  • Mice, Inbred C57BL
  • Myelin Proteins
  • Myelin Proteolipid Protein / toxicity
  • Myelin-Associated Glycoprotein / toxicity*
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / toxicity
  • Recurrence
  • Statistics, Nonparametric
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*
  • Time Factors

Substances

  • Apoproteins
  • Cytokines
  • Epitopes
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments