Although most CD8⁺ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1–self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses.

中文翻译：

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狭窄的 T 细胞受体库指导 MHC Ib 类限制性 CD8+ 调节性 T 细胞的胸腺分化

尽管大多数 CD8 ⁺ T 细胞能够杀死感染或转化的细胞，但其中一部分可以调节免疫反应并保持自我耐受。在这里，我们描述了一个 CD8 谱系，它被一组令人惊讶的限制性 T 细胞受体 (TCR) 指导分化为 CD8 T 调节细胞 (Treg)，这些受体识别 MHC-E（小鼠 Qa-1）和几种显性自肽。识别和消除表达这些 Qa-1-自肽复合物的致病性靶细胞可以选择性地抑制致病性抗体反应，而不会产生普遍的免疫抑制。使用可在体内调动 CD8 Tregs 的合成激动剂肽进行免疫，可有效抑制抗移植物抗体反应，并显着延长心脏和肾脏器官移植物的存活时间。CD8 Tregs 谱系的 TCR 依赖性分化和靶点识别的定义可能为抑制致病性抗体反应的新治疗方法开辟道路。