调节性T细胞抑制约氏疟原虫感染小鼠早期Th1应答的建立

目的探讨调节性T细胞(Tregs)参与约氏疟原虫感染早期调控Th1型免疫应答的相关机制。方法用约氏疟原虫(致死型)感染对照组和anti-CD25 mAb注射组BALB/c小鼠,计数红细胞感染率;感染后第0、3和5d制备脾细胞悬液,磁珠分选、纯化树突状细胞(DCs)并体外培养;ELISA方法检测脾细胞培养上清中IFN-γ和DCs培养上清中IL-12的水平,Griess方法检测脾细胞培养上清中NO含量。结果两组小鼠脾细胞培养上清中IFN-γ和NO水平在感染后第3～5d均明显升高,但对照组小鼠IFN-γ和NO水平明显低于anti-CD25 mAb注射组小鼠。anti-CD25 mAb注射组小鼠DCs培养上清中IL-12的水平于感染后第3d达峰值,并于感染后第5d仍维持较高水平。相比,对照组小鼠DCs培养上清中IL-12的水平仅于感染后第3d出现有意义的升高。结论Tregs在致死型约氏疟原虫感染BALB/c小鼠早期可能通过抑制DCs分泌细胞因子IL-12来抑制Th1型免疫应答的有效建立。

Regulatory T cells inhibit the development of Th1 immune responses in the early infection with Plasmodium yoelii 17XL

To investigate the related mechanism of regulatory T cells （Tregs） to regulate the Thl immune responses in the early infection with Plasrnodium yoelii 17XL, 1 × 10^6 virulent P. yoelii 17XL parasitized erythrocytes injected intraperitoneally to infect BALB/c mice injected with anti CD25 ,mAb and the control mice. The ratio of the infected RBC was counted. On days 0, 3 and 5 post infection, the dendritic cells （DCs） from spleen were purified by magnetic separation and cultured in vitro. The levels of IFN-γ in the supernatants of the cultured splenocytes and IL-12 in the supernatants of the cultured DCs were assayed with ELISA assay and the content of NO in the splenocyte supernatants was detected by Griess＇s method. It was demonstrated that the levels of both IFN-7 and NO were significantly increased in the supernatants of cultured splenocytes from two groups of BALB/c mice, but those in the control mice were comparatively lower than those of mice injected with anti-CD25 mAb. The level of IL-12 in supernatants of cultured DCs of the anti-CD25 mAb injected mice reached its peak on day 3 post-infection and maintained at a high level 5 on day after infection. In contrast, the level of IL-12 in the supernatants of cultured DCs of the control mice only showed significant increase on day 3 postinfection. These results suggest that Tregs might inhibit the effective development of the TH1 immune response at the early stage of P. yoelii 17XL infection in BALB/c mice through inhibition of secreting IL-12 from DCs.