Immunosuppression of rat myasthenia gravis by oral administration of a syngeneic acetylcholine receptor fragment.
A syngeneic rat recombinant fragment of the extracellular domain of the acetylcholine receptor (AChR) alpha-subunit (Ralpha1-205), administered orally, suppresses ongoing experimental autoimmune myasthenia gravis (EAMG) in rats. The underlying mechanism is a shift from Th1 to Th2 regulation as evidenced by downregulated mRNA expression levels of IFN-gamma and TNF-alpha, upregulated IL-10, changes in anti-AChR IgG isotypes and diminished Th1 signaling via CD28/CTLA-4:B7. Unlike the xenogeneic fragment, the syngeneic Ralpha1-205 does not induce elevation in TGF-beta and elicitation of autoregulatory cells. The ability to suppress EAMG by a non-immunogenic syngeneic fragment of AChR is encouraging and may in the future be applied for the treatment of myasthenia gravis in humans.
Maiti
Prasanta K
PK
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Feferman
Tali
T
Im
Sin-Hyeog
SH
Souroujon
Miriam C
MC
Fuchs
Sara
S
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy*; D010455:Peptides / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D010455:Peptides; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma