Th2细胞因子和抗IL-12Rβ1mAb抑制由IL-23诱导PBMCIFN-γ的产生

Inhibitory effects of Th2 cytokines and anti-IL-12Rβ1 mAbs on IL-23 inducing IFN-γ production by normal human PBMCs

目的:探讨重组人白介素23(IL-23)诱导正常人PBMC IFN-γ的产生,细胞亚群和调节因素。方法:正常人PBMC在不同条件下与IL-23进行培养,采用酶联免疫吸附试验(ELISA)检测细胞培养液中IFN-γ的水平。同时采用流式细胞仪,分析IL-23诱导PBMC IFN-γ表达的细胞亚群。结果:IL-23呈剂量依赖性诱导PBMC IFN-γ产生,并可与IL-2协同诱导IFN-γ的产生。细胞亚群分析的结果表明,IL-23诱导高表达CD56+NK细胞产生IFN-γ,对CD4+和CD8+T细胞无明显作用。Th2细胞因子和抗IL-12受体β1mAb(IL-12Rβ1)抑制IL-23诱导IFN-γ产生。结论:IL-23可直接作用于CD3-CD56+NK细胞,诱导产生IFN-γ。Th2细胞因子和抗IL-12Rβ1mAb抑制IL-23诱导IFN-γ产生,提示可以用于由IL-23引起自身免疫病的治疗。

Objective ：To evaluate the role of IL-23 in the production of IFN-γ, cell subsets and regulation by human peripheral blood mononuclear cells（PBMCs）. Methods：PBMCs were isolated from normal human peripheral blood and cultured with IL-23 in different culture conditions. The level of IFN-γ in the culture supematants was examined by ELISA. The subsets and frequency of IFN-γ-producing cells were examined at a singh cell level by flow cytometry. Results：IL-23 could directly induce IFN-γ production by PBMCs and have synergistic effect with IL-2 on the induction of IFN-γ production in a dose dependent manner. The data from Flow tyrometric analysis indicated that IL-23 could induce IFN-γ expression by CD3^＋ CD56^＋ NK cells hut not CD3^＋CD4^＋ and CD8^＋T cells. It is noted that IL-23 predominantly induced IFN-γ expression by NK cells with high expression of CD56 molecules. Addition of Th2 cytokines or anti-IL-12Rβ1 mAbs resulted in the inhibition of IL-23-inducing IFN-γ production. Conclusion： IL-23 can directly induce IFN-γ production by PBMCs. The induction of IFN-γ induced by IL-23 can be suppressed by Th2 cytokines and anti-IL-12Rβ1 mAbs. The data indicated that Th2 cytokines and anti-IL-12Rβ1 mAhs might have the potential application for the treatment of IL-23-mediated autoimmune diseases.