title: B7-1 costimulatory molecule is critical for the development of experimental autoimmune myasthenia gravis.
abstract: Following immunization with acetylcholine receptor (AChR), MHC class II-restricted, AChR-specific CD4 cell activation is critical for the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. To study the contributions of B7-1 and B7-2 costimulatory molecules in EAMG, B7-1, B7-2, and B7-1/B7-2 gene knockout (KO) mice were immunized with Torpedo AChR in CFA. Compared with wild-type C57BL6 mice, B7-1 and B7-1/2 KO mice were resistant to EAMG development. B7-1 KO mice had reduced anti-AChR Ab compared with C57BL/6 mice. However, neither B7-1 nor B7-2 gene disruption impaired AChR-induced or dominant alpha(146-162) peptide-induced in vitro lymphoproliferative responses. Blocking of the B7-1 or B7-2 molecule by specific mAbs in vivo led to a reduction in the AChR-specific lymphocyte response, and the reduction was more pronounced in mice treated with anti-B7-2 Ab. The findings implicate B7-1 molecules as having a critical role in the induction of EAMG, and the resistance of B7-1 KO mice is associated with suppressed humoral, rather than suppressed AChR-specific, T cell responses. The data also point to B7-2 molecules as being the dominant costimulatory molecules required for AChR-induced lymphocyte proliferation.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Mathilde A
authors.initials: MA
authors.lastname: Poussin
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Goluszko
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Scott
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Juan U
authors.initials: JU
authors.lastname: Franco
authors.forename: Premkumar
authors.initials: P
authors.lastname: Christadoss
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000008:administration & dosage; D006183:H-2 Antigens / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008938:Mitosis / Q000235:genetics / Q000276:immunology; D016297:Mutagenesis, Site-Directed; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D010446:Peptide Fragments / Q000276:immunology; D011978:Receptors, Nicotinic / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology
chemical_list: D019138:Antibodies, Blocking; D015703:Antigens, CD; D001323:Autoantibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016207:Cytokines; D006131:Growth Inhibitors; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011978:Receptors, Nicotinic