Down-regulation of T cell responses to AChR and reversal of EAMG manifestations in mice by a dual altered peptide ligand via induction of CD4+ CD25+ regulatory cells.
A dual altered peptide ligand (APL) composed of the tandemly arranged two single amino acid analogs of two myasthenogenic peptides, p195-212 and p259-271 was demonstrated to down-regulate in vitro and in vivo myasthenia gravis (MG) associated autoreactive responses. In this study, we demonstrate the suppressive properties of the dual APL following immunization with the whole Torpedo AChR (TAChR) and in mice with established experimental autoimmune MG (EAMG). The dual APL acts by up-regulating CD4+ CD25+ cells expressing characteristic regulatory markers along with an associated increase in levels of IL-10 and TGF-beta. The latter cytokine plays a key role in the ameliorating effects of the dual APL.
Aruna
Badiga Venkata
BV
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Sela
Michael
M
Mozes
Edna
E
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D010455:Peptides / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000276:immunology*; D013347:Subcellular Fractions; D014101:Torpedo; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015415:Biomarkers; D008024:Ligands; D010455:Peptides; D015375:Receptors, Interleukin-2; D011978:Receptors, Nicotinic; D016212:Transforming Growth Factor beta; C514281:dual altered peptide ligand; D016753:Interleukin-10