ICOS is essential for the development of experimental autoimmune myasthenia gravis.
Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant alpha146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG.
Scott
Benjamin G
BG
Department of Microbiology and Immunology, The University of Texas Medical Branch, 301 University Boulevard, 3.142 MRB, Galveston, TX 77555-1070, USA.
Yang
Huan
H
Tüzün
Erdem
E
Dong
Chen
C
Flavell
Richard A
RA
Christadoss
Premkumar
P
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D003176:Complement C3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D018858:Germinal Center / Q000378:metabolism; D007114:Immunization / Q000379:methods; D016056:Immunodominant Epitopes / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D009469:Neuromuscular Junction / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D011863:Radioimmunoassay / Q000379:methods; D011950:Receptors, Cholinergic / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014101:Torpedo
D000945:Antigens, Differentiation, T-Lymphocyte; D003176:Complement C3; D016207:Cytokines; C556694:Icos protein, mouse; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D010455:Peptides; D011950:Receptors, Cholinergic