Anti-CD3 mAb can modulate graft rejection and attenuate autoimmune diseases but their mechanism(s) of action remain unclear. CD8(+) T cells with regulatory function are induced in vitro by Teplizumab, a humanized anti-CD3 antibody and inhibit responses of autologous and allogeneic T cells. They inhibit CD4(+) T-cell proliferation by mechanisms involving TNF and CCL4, and by blocking target cell entry into G2/M phase of cell cycle but neither kill them, nor compete for IL-2. CD8(+) Treg can be isolated from peripheral blood following treatment of patients with Type 1 diabetes with Teplizumab, but not from untreated patients. The induction of CD8(+) Treg by anti-CD3 mAb requires TNF and signaling through the NF-κB cascade. The CD8(+) Treg express CD25, glucocorticoid-induced TNF receptor family, CTLA-4, Foxp3, and TNFR2, and the combined expression of TNFR2 and CD25 identifies a potent subpopulation of CD8(+) Treg. These studies have identified a novel mechanism of immune regulation by anti-CD3 mAb and markers that may be used to track inducible CD8(+) Treg in settings such as chronic inflammation or immune therapy.

中文翻译：

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用抗 CD3 抗体处理的人类 CD8(+) T 细胞获得调节功能需要 TNF。

抗 CD3 mAb 可以调节移植排斥和减轻自身免疫性疾病，但其作用机制尚不清楚。具有调节功能的 CD8(+) T 细胞由 Teplizumab 体外诱导，Teplizumab 是一种人源化抗 CD3 抗体，可抑制自体和同种异体 T 细胞的反应。它们通过涉及 TNF 和 CCL4 的机制抑制 CD4(+) T 细胞增殖，并通过阻止靶细胞进入细胞周期的 G2/M 期，但既不杀死它们，也不竞争 IL-2。用 Teplizumab 治疗 1 型糖尿病患者后，可以从外周血中分离出 CD8(+) Treg，但不能从未经治疗的患者中分离出来。抗 CD3 mAb 诱导 CD8(+) Treg 需要 TNF 和通过 NF-κB 级联的信号传导。CD8(+) Treg 表达 CD25、糖皮质激素诱导的 TNF 受体家族、CTLA-4、Foxp3 和 TNFR2，TNFR2 和 CD25 的联合表达确定了 CD8(+) Treg 的有效亚群。这些研究确定了抗 CD3 mAb 和标记物的免疫调节新机制，可用于在慢性炎症或免疫治疗等环境中追踪诱导型 CD8(+) Treg。