The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected].
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.
Penninger
J M
JM
Amgen Research Institute, Ontario Cancer Institute, Toronto, Canada.
Neu
N
N
Timms
E
E
Wallace
V A
VA
Koh
D R
DR
Kishihara
K
K
Pummerer
C
C
Mak
T W
TW
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*
D001323:Autoantibodies; D017252:CD3 Complex; D016827:CD8 Antigens; D007074:Immunoglobulin G; D009218:Myosins