Targeted Expression of Myelin Autoantigen in the Periphery Induces Antigen-Specific T and B Cell Tolerance and Ameliorates Autoimmune Disease

Front Immunol. 2021 Jun 2:12:668487. doi: 10.3389/fimmu.2021.668487. eCollection 2021.

Abstract

There is a great interest in developing antigen-specific therapeutic approaches for the treatment of autoimmune diseases without compromising normal immune function. The key challenges are to control all antigen-specific lymphocyte populations that contribute to pathogenic inflammatory processes and to provide long-term protection from disease relapses. Here, we show that myelin oligodendrocyte glycoprotein (MOG)-specific tolerance can be established by ectopic expression of MOG in the immune organs. Using transgenic mice expressing MOG-specific CD4, CD8, and B cell receptors, we show that MOG expression in the bone marrow cells results in impaired development of MOG-specific lymphocytes. Ectopic MOG expression has also resulted in long-lasting protection from MOG-induced autoimmunity. This finding raises hope that transplantation of autoantigen-expressing bone marrow cells as a therapeutic strategy for specific autoantigen-driven autoimmune diseases.

Keywords: MOG (myelin oligodendrocyte glycoprotein); autoimmunity; experimental autoimmue encephalomyelitis; multiple sclerosis (MS); tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Bone Marrow / immunology
  • Bone Marrow / metabolism*
  • Bone Marrow Transplantation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Genes, T-Cell Receptor
  • Immune Tolerance*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein / metabolism*
  • Peptide Fragments
  • Phenotype
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Mog protein, mouse
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Antigen, B-Cell
  • myelin oligodendrocyte glycoprotein (35-55)