title: The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected].
abstract: Experimental induction of most autoimmune diseases appears to depend on the activation of CD4+ T helper cells, while CD8+ lymphocytes may have a role in disease progression. To study the role of CD4+ and CD8+ T cell subsets in T cell-dependent autoimmunity, mice lacking CD4 or CD8 molecules after gene targeting were injected with cardiac myosin to induce organ specific autoimmune myocarditis. Mice homozygous for the CD8 mutation (CD8-/-) developed significantly more severe disease as compared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCR alpha beta +CD4-CD8- T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T cells has no significant influence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cells regulate disease severity and these results may explain the occurrence of autoimmunity in CD4 immunodeficiencies.
authors.affiliation: Amgen Research Institute, Ontario Cancer Institute, Toronto, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Penninger
authors.forename: N
authors.initials: N
authors.lastname: Neu
authors.forename: E
authors.initials: E
authors.lastname: Timms
authors.forename: V A
authors.initials: VA
authors.lastname: Wallace
authors.forename: D R
authors.initials: DR
authors.lastname: Koh
authors.forename: K
authors.initials: K
authors.lastname: Kishihara
authors.forename: C
authors.initials: C
authors.lastname: Pummerer
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D006720:Homozygote; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D009218:Myosins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D017252:CD3 Complex; D016827:CD8 Antigens; D007074:Immunoglobulin G; D009218:Myosins