INDUCTION OF EXPERIMENTAL AUTOIMMUNE MYOCARDITIS IN MICE LACKING CD3 OR CD8 MOLECULES

Experimental induction of most autoimmune diseases appears to depend o n the activation of CD4+ T helper cells, while CD8+ lymphocytes may ha ve 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 CD 8 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 c ompared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCRalphabeta+CD4-CD8-T cel ls in the heart tissue and appearance of autoantibodies. These data de monstrate that the lack of CD4+ or CD8+ T cells has no significant inf luence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cell s regulate disease severity and these results may explain the occurren ce of autoimmunity in CD4 immunodeficiencies.