The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected].
The induction of experimental autoimmune myocarditis in mice lacking CD4 or CD8 molecules [corrected].
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DOI：
10.1084/jem.178.5.1837
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发表时间：
1993-11-01
期刊：
影响因子：
--
通讯作者：
Mak TW
中科院分区：
文献类型：
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作者：
Penninger JM;Neu N;Timms E;Wallace VA;Koh DR;Kishihara K;Pummerer C;Mak TW
大多数自身免疫性疾病的实验诱导似乎依赖于CD 4 + T辅助细胞的活化，而CD 8+淋巴细胞可能在疾病进展中起作用。为研究CD 4+和CD 8 + T细胞亚群在T细胞依赖性自身免疫中的作用，采用基因打靶法建立了CD 4或CD 8分子缺失的小鼠心肌肌球蛋白模型，诱导器官特异性自身免疫性心肌炎。与CD 4 +/-CD 8 +/-对照组相比，CD 8突变纯合子（CD 8-/-）小鼠发生了显著更严重的疾病。令人惊讶的是，CD 4-/-小鼠发生自身免疫性心肌炎，心脏组织中有TCR α β + CD 4-CD 8- T细胞浸润，并出现自身抗体。这些数据表明，缺乏CD 4+或CD 8 + T细胞对自身免疫性心肌炎的发生没有显着影响。CD 4+和CD 8+细胞调节疾病的严重程度，这些结果可以解释在CD 4免疫缺陷的自身免疫的发生。
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.