Vitiligo is an autoimmune disease of the skin mediated by CD8⁺ T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (T_RM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)–deficient mice reportedly have impaired T_RM formation, and IL-15 promotes T_RM function ex vivo. We found that both human and mouse T_RM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits T_RM production of interferon-γ (IFNγ), and long-term treatment depletes T_RM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving T_RM.

^{白癜风是一种由 CD8 +} T 细胞介导的皮肤自身免疫性疾病，可杀死黑色素细胞并产生白斑。白癜风的皮肤损伤在停止常规治疗后经常复发，这支持了在这些部位形成自身免疫记忆的假设。我们发现患有白癜风的小鼠和人类中的病变 T 细胞显示出常驻记忆 (T _RM ) 表型，类似于那些提供快速、局部保护以防止皮肤和粘膜嗜性病毒再次感染的表型。据报道，白细胞介素 15 (IL-15) 缺陷小鼠的 T _RM形成受损，而 IL-15 在离体促进 T _RM功能。我们发现人类和小鼠 T _RM表达 IL-15 受体的 CD122 亚基，角质形成细胞上调 CD215，CD215 是在其表面展示细胞因子以促进 T 细胞活化所需的亚基。用抗 CD122 抗体靶向 IL-15 信号可以逆转已确诊白癜风的小鼠的疾病。用抗 CD122 进行短期治疗会抑制 T _RM产生干扰素-γ (IFNγ)，而长期治疗会耗尽皮肤损伤中的 T _RM。使用抗 CD122 进行短期治疗可以在全身或局部皮肤给药时提供持久的色素沉着。_{基于这些数据，我们提出靶向 CD122 可能是治疗白癜风和其他涉及 T RM}的组织特异性自身免疫性疾病的高效甚至持久的治疗策略。