title: Fas/Fas ligand pathway, apoptosis, and clonal anergy involved in systemic acetylcholine receptor T cell epitope tolerance.
abstract: The cellular mechanisms of high dose systemic acetylcholine receptor (AChR) T cell epitope, alpha 146--162 peptide-induced tolerance in experimental myasthenia gravis were examined. CD4 cells are the prime target for alpha 146--162 peptide-induced tolerance. The expression of CD69, Fas, and B7.2 molecules on AChR-immune lymphocytes was enhanced within 4--12 h after tolerance induction. A high dose of alpha 146--162 peptide in IFA failed to suppress T cell proliferation and/or clinical myasthenia gravis in lpr and gld mice deficient in Fas and Fas ligand, respectively. A high dose of alpha 146--162 peptide in IFA in AChR-immunized mice induced apoptosis of BV6 cells. Further, reconstitution of IL-2 in vitro-recovered alpha 146--162 peptide tolerized T cell proliferation, IFN-gamma, and IL-10 production. The findings implicate the possible role of Fas-/Fas ligand-mediated apoptosis and the resulting clonal anergy as the mechanisms of high dose AChR alpha 146--162 peptide-induced tolerance on CD4 cells.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: C
authors.initials: C
authors.lastname: Deng
authors.forename: E
authors.initials: E
authors.lastname: Goluszko
authors.forename: P
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D053222:Fas Ligand Protein; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007700:Kinetics; D037181:Lectins, C-Type; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014101:Torpedo; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000099192:CD69 Antigens
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001323:Autoantibodies; D051940:B7-2 Antigen; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D053222:Fas Ligand Protein; D005620:Freund's Adjuvant; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011950:Receptors, Cholinergic; D019014:fas Receptor; D000099192:CD69 Antigens; C497965:Cd86 protein, mouse; C505658:Fasl protein, mouse