CD226 deficiency attenuates the homeostasis and suppressive capacity of Tr1 cells.

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.