CD137信号下调乳腺癌患者外周血Treg细胞的免疫抑制功能

CD137 Signaling Suppresses the Suppressive Function of Treg Cells of Peripheral Blood from Breast Cancer Patients

目的探讨CD137信号对CD4^+CD25^+调节性T细胞(Treg)的生物学效应及机制。方法采用激发型抗人CD137单抗加入PHA刺激的乳腺癌患者外周血T细胞培养体系及Treg细胞培养体系中,利用细胞计数及~3H-TdR掺入法分析T细胞的增殖,流式细胞术分析细胞膜分子和Foxp3表达,ELISA分析细胞因子的分泌。结果CD137分子表达于乳腺癌患者外周血CD4^+CD25^+Treg细胞膜;抗人CD137单抗加入PHA活化的乳腺癌患者T细胞培养体系后,T细胞增殖明显增加,Foxp3^+Treg细胞比例明显下降;激发CD137信号可下调CD4^+CD25^+Treg细胞的Foxp3表达,抑制Treg细胞产生TGF-β1和IL-10,以及下调Treg细胞对PHA刺激的CD4^+CD25^-T细胞增殖的抑制效应。结论CD137信号可抑制Treg细胞的免疫抑制功能,CD137可能是对Treg细胞进行免疫干预的重要靶点。

Objective To explore the biological effect of CD137 and its molecular mechanism on CD4 ^＋ CD25^ Treg cells. Methods Anti-CD137 mAb was added to stimulate the T cells that isolated from peripheral blood of breast cancer patients and activated by PHA. T cell proliferation was determined by cell counting or by ^3H-TdR incorporation assessing at the 3rd. The phenotype of cells was determined by FACS, and Foxp3 analysis was performed after fixation and intracellular staining. Cytokine in the super- natant was quantified with ELISA. Results CD137 expressed on CD4 ^＋ CD25^＋Treg cells. Triggering CD137 signaling of CD4^＋ CD25^＋ Treg cells by anti-CD137 mAb could promote the proliferation of T cells form PBMCs of breast cancer patients and decrease the ratio of Foxp3 ^ Treg population and reduce Foxp3 expression of Treg cells, as well as the production of TGF-β1 and IL-10, and suppress the ability of Treg cells to inhibit proliferation of CD4^＋ CD25^＋ cells. Conclusion CD137 signaling could suppress the suppressive function of Treg cells, and CD137 might be a potential molecular target for the immunological interference.