细胞因子直接诱导正常人CD4^+T细胞产生IL-17和IFN-γ

The role of cytokines in the production of IL-17 and IFN-γ via the induction of normal human peripheral blood mononuclear cells and CD4^+T cells

目的:探讨细胞因子(IL-23、IL-2和IL-15)对正常人外周血单个核细胞(PBMC)和CD4+T细胞IL-17产生的诱导作用和调节因素。方法:将正常人PBMC和纯化的CD4+T细胞在不同条件下与IL-23、IL-2和IL-15进行培养,采用ELISA法检测细胞培养液中IL-17和IFN-γ的水平;采用酶联免疫斑点试验(ELISPOT)在单个细胞水平上检测IL-17和IFN-γ产生细胞的频率。结果:IL-23可诱导PBMC产生IL-17和IFN-γ;Th2细胞因子和抗IL-12受体β1(IL-12Rβ1)mAb可抑制IL-23诱导的IL-17和IFN-γ产生。IL-2和IL-15均可诱导IL-17和IFN-γ产生,并与IL-23具有共同诱导作用。IL-12可诱导PBMC产生大量的IFN-γ,但不产生IL-17。进一步研究表明,IL-23、IL-2和IL-15可直接诱导纯化的CD4+T细胞产生IL-17和IFN-γ。结论:IL-23、IL-2和IL-15可直接作用于正常人CD4+T细胞诱导其产生IL-17和IFN-γ;Th2细胞因子和抗IL-12Rβ1mAb可抑制IL-23诱导的IL-17和IFN-γ产生。为探讨自身免疫性疾病等的发生机制和治疗提供了新的靶点。

AIM： To investigate the role of cytokines （IL-23, IL-2 and IL-15） in the production and regulation of IL-17 and IFN-3, via the induction of normal human peripheral blood mononuclear cells （PBMCs） and CD4^＋ T cells. METHODS： PBMCs or CD4^＋T cells from normal human blood were cultured with IL-23, IL-2 or IL-15 in the presence or absence of IL-23. The level of IL-17 and IFN-3, in the culture supematants was assessed by ELISA. The frequency of IL-17 and IFN-3, produced cells was detected by ELlS- POT. RESULTS： IL-23 induced PBMCs to produce IL-17 and IFN-γ. IL-2 and IL-15 induced the production of IL-17 and IFN-γ, in a dose dependent manner by PBMCs. Similar results were confirmed by ELISPOT assay. The addition of Th2 cytokines （ IL-4 and IL-10） or anti-lL-12RIS1 mAbs resulted in the inhibition of IL-17 and IFN-γ production induced by IL-23. Further study suggested that IL-23, IL-2 and IL-15 directly induced the production of IL-17 and IFN-h, by purified CD4^＋T cells. CONCLUSION： IL-23, IL-2 and IL-15 can di- rectly induce CD4^＋T cells to produce IL-17 and IFN-h,. The production of IL-17 and IFN-γ induced by IL-23 can be inhibi- ted by Th2 cytokines and anti-lL-12RIS1 mAbs. The finding of our research may provide some new targets for the study of mechanism and treatment of IL-17-mediated autoimmune diseases.