Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo. CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.

白癜风是一种以黑色素细胞破坏为特征的自身免疫性皮肤病。白癜风皮肤中的调节性 T 细胞 (Tregs) 大大减少，补充外周皮肤 Tregs 可以防止色素脱失。神经节苷脂 D3 (GD3) 被包括黑素细胞在内的病灶周围表皮细胞过度表达，这促使我们产生 GD3 反应性嵌合抗原受体 (CAR) Tregs 来治疗白癜风。小鼠接受未转导的 Tregs 或 GD3 特异性 Tregs 以检验抗原特异性有助于降低自身免疫反应性的假设体外和体内. 在自发性白癜风的 TCR 转基因小鼠模型中，与未转导的 Tregs 和载体对照受体相比，CAR Tregs 显示出响应抗原的 IL-10 分泌增加，对黑素细胞的细胞毒性提供了更好的控制，并支持显着延迟脱色。与两个对照组相比，后一项发现与治疗小鼠中更多丰富的 Tregs 和黑素细胞有关。我们的数据支持可以制备、使用和储存抗原特异性 Treg 以长期控制进行性脱色的概念。