Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis.
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.
Sheng
Jian Rong
JR
Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago, IL-60612, USA.
Li
Liang Cheng
LC
Ganesh
Balaji B
BB
Prabhakar
Bellur S
BS
Meriggioli
Matthew N
MN
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D002455:Cell Division; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D000906:Antibodies; D011950:Receptors, Cholinergic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor