The T cell response to central nervous system (CNS) antigen in experimental autoimmune encephalomyelitis (EAE) permits one to model the immune aspects of multiple sclerosis. 1C6 transgenic mice on the non-obese diabetic (NOD) background possess a class II-restricted T cell receptor (TcR; Vα5-Vβ7) specific for the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)_[35−55]. It remains to be determined what role is played by allelic inclusion in shaping the TcR repertoire of these mice. Here, we show that 1C6 T cells display substantial promiscuity in their expression of non-transgenically derived Vα chains. Further, enforced expression of the transgenic TcR in 1C6 × Rag1^−/− mice profoundly disrupted thymic negative selection and led to a sharp decrease in the number of mature peripheral T cells. 1C6 × Rag1^−/− mice developed spontaneous EAE at a significant frequency and rapidly developed fatal EAE upon immunization with myelin oligodendrocyte glycoprotein (MOG)_[35−55]. Passive transfer of 1C6 × Rag1^+/+ CD4⁺ T cells, but not CD8⁺ T cells or B cells, partially rescued 1C6 × Rag1^−/− mice from severe EAE. FoxP3⁺ CD4⁺ T_reg cells were present in the CNS of immunized 1C6 mice, as well as immunized 1C6 × Rag1^−/− that had been supplemented with 1C6 CD4⁺ T cells. However, they were not observed in 1C6 × Rag1^−/− that did not receive Rag1-sufficient 1C6 CD4⁺. Further, in vivo blockade of T_reg accelerated the onset of symptoms in 1C6 mice immunized with MOG_[35−55], indicating the pertinence of T_reg-mediated control of autoimmune inflammation in this model. Thus, TcR allelic inclusion is crucial to the generation of FoxP3⁺ CD4⁺ T cells necessary for the suppression of severe CNS autoimmunity.

在实验性自身免疫性脑脊髓炎（EAE）中，T细胞对中枢神经系统（CNS）抗原的反应使人们能够模拟多发性硬化症的免疫方面。在非肥胖糖尿病（NOD）背景下的1C6转基因小鼠具有II型限制性T细胞受体（TcR;Vα5-Vβ7），其特异性针对脑病原性肽髓磷脂少突胶质糖蛋白（MOG）_[35-55]。尚待确定等位基因包涵体在塑造这些小鼠的TcR库中起什么作用。在这里，我们显示1C6 T细胞在其非转基因来源的Vα链的表达中显示出大量的混杂。此外，转基因TcR在1C6×中的强制表达破布1^-/-小鼠极大地破坏了胸腺的阴性选择，并导致成熟的外周血T细胞数量急剧减少。1C6×破布1^-/-小鼠以髓鞘少突胶质细胞糖蛋白（MOG）免疫后，以明显的频率自发产生EAE，并迅速产生致命性EAE _[35-55]。被动转移1C6×破布1^{+ / +} CD4 ⁺ T细胞，而非CD8 ⁺ T细胞或B细胞，部分获救1C6×破布1来自严重EAE的^-/-小鼠。FoxP3 ⁺ CD4 ⁺ T _reg细胞存在于1C6免疫小鼠和1C6×破布1^-/-已经补充了1C6 CD4 ⁺ T细胞。但是，在1C6中未观察到它们×破布1没有收到Rag1足够的1C6 CD4 ^+的-/-。进一步，体内T _reg的阻断加速了用MOG免疫的1C6小鼠的症状发作_[35-55]，表明该模型中T _reg介导的自身免疫炎症控制的相关性。因此，TcR等位基因包涵对于抑制严重的CNS自身免疫所必需的FoxP3 ⁺ CD4 ⁺ T细胞的产生至关重要。