Treatment with anti-CD3 mAb modulates immune responses that cause type 1 diabetes and other diseases. CD8+ Tregs can be induced in vitro and in vivo by mAb. However, 1/3 of patients do not respond to drug therapy and in an equal proportion, anti-CD3 mAb does not induce Tregs in vitro. The acquisition of CD8+ Treg activity is a function of the CD8+ cells and not the targets in the assay. To identify markers to differentiate responses of CD8+ Tregs, we analyzed genes differentially expressed in CD8+ T cells of non-responders compared with responders, and found that an inhibitory receptor NKG2A (CD159a) was highly expressed in cells from all non-responders tested. Application of a mAb agonistic to NKG2A during in vitro CD8+ Treg induction by anti-CD3 prevented induction of CD8+ Tregs. CD8+ T cells that are TNFR2+ but NKG2A- are the most potently induced Tregs. The level of NKG2A expression on resting CD8+ T cells inversely correlated with acquisition of regulatory function when activated. We suggest that the induction of human CD8+ Tregs by anti-CD3 mAb is controlled by a negative signaling through NKG2A, and that NKG2A may serve as a negative marker of human CD8+ Tregs.

中文翻译：

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NKG2A 是通过抗 CD3 抗体激活的人类 CD8+ T 细胞获得调节功能的标志物。

抗 CD3 mAb 治疗可调节导致 1 型糖尿病和其他疾病的免疫反应。CD8+ Tregs 可以在体外和体内被 mAb 诱导。然而，1/3 的患者对药物治疗没有反应，同样比例的抗 CD3 mAb 不会在体外诱导 Tregs。CD8+ Treg 活性的获得是 CD8+ 细胞的功能，而不是测定中的目标。为了鉴定区分 CD8+ Tregs 反应的标记物，我们分析了与反应者相比，在无反应者的 CD8+ T 细胞中差异表达的基因，发现抑制性受体 NKG2A (CD159a) 在所有测试的无反应者的细胞中高度表达。在抗 CD3 的体外 CD8+ Treg 诱导期间对 NKG2A 应用 mAb 激动剂阻止了 CD8+ Treg 的诱导。为 TNFR2+ 但为 NKG2A- 的 CD8+ T 细胞是最有效诱导的 Treg。静息 CD8+ T 细胞上的 NKG2A 表达水平与激活时获得的调节功能呈负相关。我们认为抗 CD3 mAb 对人 CD8+ Treg 的诱导受通过 NKG2A 的负信号控制，并且 NKG2A 可作为人 CD8+ Treg 的阴性标志物。