IL-4、IL-10和抗IL-12受体β1mAb抑制IL-23诱导正常人记忆T细胞IFN-γ产生

Inhibitory effects of IL-4, IL-10, and anti-IL-12Rβ1 mAbs on the production of IL-23-inducing IFN-γ by activated normal human memory T cells

目的探讨重组人白介素23(IL23)是否能够诱导正常人T细胞IFNγ的产生,作用的靶细胞亚群和调节因素。方法正常人PBMC在抗CD3(antiCD3)单克隆抗体或antiCD3和抗CD28(antiCD28)单克隆抗体刺激的条件下与IL23进行培养,采用酶联免疫吸附试验(ELISA)检测细胞培养液中IFNγ的水平;同时采用流式细胞仪,在单个细胞水平上分析IL23诱导PBMCIFNγ表达的T细胞亚群。结果在未经任何刺激的情况下,PBMC产生很低或不产生IFNγ。IL23呈剂量依赖方式促进由antiCD3活化的PBMCIFNγ产生。细胞亚群分析的结果表明,IL23诱导记忆CD4+和CD8+T细胞表达IFNγ,对活化的CD4+T细胞作用较为明显。Th2细胞因子(IL4、IL10)和抗IL12受体β1mAb(IL12Rβ1)抑制IL23诱导T细胞IFNγ产生。结论IL23促进活化的记忆CD4+和CD8+T细胞IFNγ的产生。Th2细胞因子和抗IL12Rβ1mAb抑制由IL23诱导IFNγ产生,提示这些细胞因子和抗体对IL23引起的自身免疫病具有拮抗作用。

Objective To evaluate the role of IL-23 in the IFN-γ production by activated human peripheral blood mononuclear cells （PBMCs）. Methods PBMCs were isolated from normal human peripheral blood and cultured with anti-CD3 mAb or anti-CD3 plus anti-CD28 mAb in the presence or absence of IL-23. The level of IFN-γ in the culture supernatants was assessed by ELISA. The subsets and frequency of IFN-γ-producing cells were examined at a single cell level by flow cytometry. Results IL-23 enhanced IFN-γ production by anti-CD3- or anti- CD3 plus anti-CD28 mAb-stimulated PBMCs in a dose-dependent manner. The data from flow cytometric analysis indicated that IL-23 could enhance IFN-γ expression by activated memory CD4^＋ and CD8^＋ T cells. Addition ofTh2 cytokines （IL-4 and IL-10） or anti-IL-12Rβ1 mAbs resulted in the inhibition of IL-23-inducing IFN-γ production. Conclusion IL-23 could promote IFN-γ production by activated memory T cells. The production of IFN-γ induced by IL-23 can be suppressed by Th2 cytokines and anfi-IL-12Rβ1 mAbs, indicating that Th2 cytokines and antiIL-12Rβ1 mAbs might have the potential application for the treatment of IL-23-mediated antoimmune diseases.