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 TCRαβ+CD4−CD8− T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T ceils 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. © 1993, Rockefeller University Press., All rights reserved.