title: GM-CSF-induced regulatory T cells selectively inhibit anti-acetylcholine receptor-specific immune responses in experimental myasthenia gravis.
abstract: We and others have demonstrated the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to suppress autoimmunity by increasing the number of CD4(+)CD25(+) regulatory T cells (Tregs). In the current study, we have explored the critical role of induced antigen specific Tregs in the therapeutic effects of GM-CSF in murine experimental autoimmune myasthenia gravis (EAMG). Specifically, we show that Tregs from GM-CSF treated EAMG mice (GM-CSF/AChR-induced-Tregs) adoptively transferred into animals with EAMG suppressed clinical disease more potently than equal numbers of Tregs from either GM-CSF untreated EAMG mice or healthy mice treated with GM-CSF. In addition, GM-CSF/AChR-induced-Tregs selectively suppressed antigen specific T cell proliferation induced by AChR relative to that induced by an irrelevant self antigen, (thyroglobulin) and failed to significantly alter T cell proliferation in response to an exogenous antigen (ovalbumin). These results are consistent with the hypothesized mechanism of action of GM-CSF involving the mobilization of tolerogenic dendritic cell precursors which, upon antigen (AChR) capture, suppress the anti-AChR immune response through the induction/expansion of AChR-specific Tregs.
authors.affiliation: Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago, IL-60612, United States.
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.forename: Thiruppathi
authors.initials: T
authors.lastname: Muthusamy
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Meriggioli
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D049109:Cell Proliferation; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology* / Q000627:therapeutic use; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D011950:Receptors, Cholinergic / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation
chemical_list: D001323:Autoantibodies; D018680:Cholinergic Antagonists; D011950:Receptors, Cholinergic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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