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
References
Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·A MillerH L Weiner
Feb 1, 1992·Journal of Autoimmunity·M BelloneB M Conti-Tronconi
Aug 1, 1986·Immunobiology·O Axelrod, E Mozes
Dec 1, 1988·The Journal of Clinical Investigation·S BrockeE Mozes
Jan 1, 1988·Advances in Immunology·J LindstromY Fujii
Aug 1, 1994·Cellular Immunology·S L KirshnerE Mozes
Sep 1, 1994·Cellular Immunology·Z Y WangT Olsson
Sep 1, 1994·Cellular Immunology·L M SantosH L Weiner
Apr 1, 1995·Journal of Neuroimmunology·C G MaH Link
Feb 1, 1995·The Journal of Experimental Medicine·D GuN Sarvetnick
Sep 1, 1994·Neurology·R AhlbergA K Lefvert
Nov 1, 1994·Annals of Neurology·S OkumuraD B Drachman
May 1, 1994·Journal of Neuroimmunology·J LinkH Link
Jun 23, 1994·The New England Journal of Medicine·D B Drachman
Nov 1, 1993·European Journal of Immunology·M BiffenD R Alexander
May 1, 1993·Journal of Neuroimmunology·Z Y WangH Link
Jan 25, 1996·Nature·S BrockeL Steinman
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y Katz-LevyE Mozes
Aug 4, 1997·The Journal of Experimental Medicine·B BalasaN Sarvetnick
Aug 1, 1997·Journal of Autoimmunity·M PolanskiH L Weiner
Oct 23, 1997·Journal of the Neurological Sciences·R WeissertH Link
Jul 1, 1998·Clinical Immunology and Immunopathology·V DedhiaP Christadoss
Jun 23, 1999·Journal of Neuroimmunology·P I KarachunskiB M Conti-Fine
Nov 11, 1999·Clinical and Experimental Immunology·Y M HuangH Link
Nov 5, 1999·The Journal of Clinical Investigation·F BaggiC Antozzi
Feb 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·M Paas-RoznerE Mozes
Apr 26, 2000·Clinical Immunology : the Official Journal of the Clinical Immunology Society·H B WangH Link
Feb 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·A QuinnE E Sercarz
Apr 3, 2001·Journal of Neuroimmunology·J St LouisG H Strejan
Jun 8, 2001·The Journal of Experimental Medicine·E M Shevach
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
Dec 10, 2008·Expert Opinion on Biological Therapy·Darja Kanduc
Nov 8, 2008·Expert Opinion on Biological Therapy·Maria KatsaraVasso Apostolopoulos
Sep 14, 2013·Journal of Neuroimmunology·Arunakumar GangaplaraJay Reddy
May 26, 2007·Scandinavian Journal of Immunology·H Ben-DavidE Mozes
Jul 11, 2006·Immunology·Badiga Venkata ArunaEdna Mozes
May 27, 2010·Diabetes/metabolism Research and Reviews·Timo Burster, Bernhard O Boehm
Jun 15, 2004·Neurobiology of Disease·Rui-Sheng DuanBao-Guo Xiao
Jun 29, 2004·Human Immunology·Molly DayanEdna Mozes
Jun 8, 2006·Journal of Neuroimmunology·Badiga Venkata ArunaEdna Mozes
May 13, 2015·Clinical and Experimental Medicine·Yong ZhangDeqin Geng
Apr 14, 2015·Journal of Neuroimmunology·Hua XuRui-Sheng Duan
Oct 1, 2004·Arthritis and Rheumatism·L K MyersA H Kang
Mar 6, 2018·BMC Medical Genomics·Olga V SaikVladimir A Ivanisenko
Oct 3, 2002·Nature Reviews. Immunology·Angela Vincent
Dec 18, 2020·Frontiers in Neurology·Konstantinos Lazaridis, Socrates J Tzartos