T regulatory type 1 (Tr1) cells act as a key regulator in maintaining peripheral immune tolerance. Several costimulatory molecules for T cells have been identified in Tr1 cells, but their intrinsic functions are still unclear. Here we showed CD226 was highly expressed in Tr1 cells. CD226-deficient Tr1 cells were defective in proliferation and sensitive to apoptosis. In addition, CD226-deficient Tr1 cells showed lower inhibitory capacity of T cell proliferation and reduced IL-10 production. CD226 deficiency also inhibited Tr1 cell differentiation in vitro. When stimulated with IL-2, CD226-deficient Tr1 cells showed impaired STAT5 signaling. Therefore, our data suggest CD226 might play an important role in Tr1 cell homeostasis, function and differentiation. This study facilitates further biological characterization of this regulatory T cell subset.

T调节型1（Tr1）细胞在维持外周免疫耐受中起关键调节剂的作用。Tr1细胞中已经鉴定出几种T细胞共刺激分子，但它们的内在功能尚不清楚。在这里，我们显示CD226在Tr1细胞中高度表达。CD226缺陷的Tr1细胞在增殖方面有缺陷，并且对凋亡敏感。此外，CD226缺陷的Tr1细胞显示出较低的T细胞增殖抑制能力，并降低了IL-10的产生。CD226缺乏症在体外也抑制Tr1细胞分化。当用IL-2刺激时，CD226缺陷的Tr1细胞显示出STAT5信号传导受损。因此，我们的数据表明CD226可能在Tr1细胞的稳态，功能和分化中起重要作用。这项研究促进了这种调节性T细胞亚群的进一步生物学表征。