Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis.
Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis.
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DOI：
10.1084/jem.188.10.1883
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发表时间：
1998-11-16
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T细胞介导的自身免疫性疾病的发展取决于效应和调节机制之间的平衡。使用两个表达相同髓鞘碱性蛋白（MBP）特异性T细胞受体（TCR）基因的转基因小鼠品系，我们先前已经证明，仅携带MBP特异性T细胞（指定为T/R-）的小鼠自发地发生实验性自身免疫性脑脊髓炎（EAE），而携带MBP特异性T细胞以及其他淋巴细胞（指定为T/R+）的小鼠则不会发生。在这里，我们证明了T/R−小鼠可以通过早期转移正常供体的总脾细胞或纯化的CD 4 + T细胞来保护其免受EAE的影响。此外，T/R+小鼠与B细胞缺陷型、γ/δ T细胞缺陷型或主要组织相容性复合物I类缺陷型小鼠杂交后不会自发发生EAE，而T/R+小鼠与TCR-α和-β基因敲除小鼠杂交后发生EAE的发生率和严重程度与T/R−小鼠相同。此外，仅缺乏内源性TCR-α链的MBP特异性转基因小鼠发生EAE的发生率高，但严重程度降低。令人惊讶的是，三分之二的仅缺乏内源性TCR-β链的MBP特异性转基因小鼠也发生了EAE，这表明在T/R+小鼠中，具有高保护活性的细胞逃避了TCR-β链等位基因排斥。我们的研究鉴定了携带内源性α和β TCR链的CD 4 + T细胞作为预防T/R+小鼠自发性EAE的淋巴细胞。
The development of T cell–mediated autoimmune diseases hinges on the balance between effector and regulatory mechanisms. Using two transgenic mouse lines expressing identical myelin basic protein (MBP)–specific T cell receptor (TCR) genes, we have previously shown that mice bearing exclusively MBP-specific T cells (designated T/R−) spontaneously develop experimental autoimmune encephalomyelitis (EAE), whereas mice bearing MBP-specific T cells as well as other lymphocytes (designated T/R+) did not. Here we demonstrate that T/R− mice can be protected from EAE by the early transfer of total splenocytes or purified CD4+ T cells from normal donors. Moreover, whereas T/R+ mice crossed with B cell–deficient, γ/δ T cell–deficient, or major histocompatibility complex class I–deficient mice did not develop EAE spontaneously, T/R+ mice crossed with TCR-α and -β knockout mice developed EAE with the same incidence and severity as T/R− mice. In addition, MBP-specific transgenic mice that lack only endogenous TCR-α chains developed EAE with high incidence but reduced severity. Surprisingly, two-thirds of MBP-specific transgenic mice lacking only endogenous TCR-β chains also developed EAE, suggesting that in T/R+ mice, cells with high protective activity escape TCR-β chain allelic exclusion. Our study identifies CD4+ T cells bearing endogenous α and β TCR chains as the lymphocytes that prevent spontaneous EAE in T/R+ mice.