Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis

Clin Immunol. 2008 Aug;128(2):172-80. doi: 10.1016/j.clim.2008.03.509. Epub 2008 May 27.

Abstract

We had previously observed that treatment utilizing granulocyte-macrophage colony-stimulating factor (GM-CSF) had profound effects on the induction of experimental autoimmune myasthenia gravis (EAMG), a well-characterized antibody-mediated autoimmune disease. In this study, we show that EAMG induced by repeated immunizations with acetylcholine receptor (AChR) protein in C57BL6 mice is effectively suppressed by GM-CSF treatment administered at a stage of chronic, well-established disease. In addition, this amelioration of clinical disease is accompanied by down-modulation of both autoreactive T cell, and pathogenic autoantibody responses, a mobilization of DCs with a tolerogenic phenotype, and an expansion of regulatory T cells (Tregs) that potently suppress AChR-stimulated T cell proliferation in vitro. These observations suggest that the mobilization of antigen-specific Tregs in vivo using pharmacologic agents, like GM-CSF, can modulate ongoing anti-AChR immune responses capable of suppressing antibody-mediated autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / blood
  • Antibodies / immunology
  • Antibody Specificity
  • Cell Division
  • Chronic Disease
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Myasthenia Gravis, Autoimmune, Experimental / blood
  • Myasthenia Gravis, Autoimmune, Experimental / drug therapy
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Receptors, Cholinergic / immunology
  • T-Lymphocytes, Regulatory / physiology

Substances

  • Antibodies
  • Receptors, Cholinergic
  • Granulocyte-Macrophage Colony-Stimulating Factor