The nature of the active suppression of responses associated with experimental autoimmune myasthenia gravis by a dual altered peptide ligand administered by different routes

Proceedings of the National Academy of Sciences of the United States of America
M Paas-RoznerE Mozes

Abstract

Myasthenia gravis (MG) and experimental autoimmune MG (EAMG) are T-cell regulated, antibody-mediated diseases. Peptides p195-212 and p259-271 of the human acetylcholine receptor (AChR) alpha-subunit, were previously shown to be immunodominant T cell epitopes in MG patients as well as in SJL and BALB/c mice, respectively. A dual altered peptide ligand (APL) composed of the two single amino acid analogs of the myasthenogenic peptides was shown to inhibit, in vitro and in vivo, MG-associated autoimmune responses. Furthermore, the dual APL was shown to down-regulate the clinical manifestations of an established EAMG in C57BL/6 mice injected with Torpedo AChR (TAChR). In the present study we attempted the elucidation of the mechanism(s) by which the dual APL down-regulates EAMG-associated responses. It is shown here that the dual APL acts by actively suppressing, in a specific manner, myasthenogenic T cell responses. The active suppression is mediated, at least partially, by the up-regulation of the secretion of TGF-beta following administration of the dual APL. The up-regulated secretion of TGF-beta is accompanied by down-regulation of IFN-gamma and IL-2 [T helper (Th) 1-type cytokine] secretion and by an up-regulation of IL-10 sec...Continue Reading

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Citations

Dec 17, 2002·Arthritis and Rheumatism·Linda K MyersAndrew H Kang
Nov 19, 2002·Journal of Neurobiology·Jon Lindstrom
Jun 6, 2007·Current Allergy and Asthma Reports·Stephen Reddel
Jul 12, 2002·Drug Discovery Today·Michael SelaBilha Schechter
Apr 7, 2005·Nature Medicine·Mark Larché, David C Wraith
Apr 13, 2006·Rejuvenation Research·Michael Sela
Oct 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Hava Ben-DavidEdna Mozes
May 14, 2003·Proceedings of the National Academy of Sciences of the United States of America·Miri Paas-RoznerEdna Mozes
Jul 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Badiga Venkata ArunaEdna Mozes
Nov 17, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hava Ben-DavidEdna Mozes
Aug 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Michael Sela, Edna Mozes
Jan 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hava Ben-DavidEdna Mozes
May 15, 2015·International Reviews of Immunology·Evan L SauerJudith M Greer
Nov 8, 2008·Expert Opinion on Biological Therapy·Maria KatsaraVasso Apostolopoulos
Oct 1, 2004·Arthritis and Rheumatism·L K MyersA H Kang
Oct 3, 2002·Nature Reviews. Immunology·Angela Vincent
Dec 18, 2020·Frontiers in Neurology·Konstantinos Lazaridis, Socrates J Tzartos

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