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.
The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected]
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J M Penninger, N Neu, E Timms, V A Wallace, D R Koh, K Kishihara, C Pummerer, T W Mak; The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected]. J Exp Med 1 November 1993; 178 (5): 1837–1842. doi: https://doi.org/10.1084/jem.178.5.1837
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