4+CD25+Foxp3+调节性T细胞在脑型疟疾发生中的作用研究
Research on the role of CD4+CD25+Foxp3+regulatory T cells in the occurrence of experimental cerebral malaria
为探讨调节性T细胞(regulatory T cells, Tregs)在脑型疟疾(cerebral malaria, CM)中的活化特点及其与疾病进展的相关性,用P. berghei ANKA(P.bANKA)分别感染C57BL/6和BALB/c小鼠,计数红细胞感染率;感染前和感染后3、5、8d制备脾细胞悬液,流式细胞术检测脾细胞悬液中Tregs数量;ELISA方法检测脾细胞培养上清IFN-γ与IL-10水平。C57BL/6小鼠感染后8~11d死于CM,BALB/c小鼠感染后3~4w死于贫血和过度虫体血症。两种小鼠于感染后3d,Tregs绝对数达到峰值后逐渐下降,于感染后8d,C57BL/6小鼠Tregs数量下降最为显著并明显低于正常水平,并且整个感染过程中其数量显著低于BALB/c小鼠。两种小鼠脾细胞培养上清IFN-γ和IL-10水平于感染后开始升高,感染后5d达到峰值,感染后8d与感染后5d相比,C57BL/6小鼠IFN-γ水平轻微下降,IL-10水平显著下降;BALB/c小鼠呈相反变化。并且C57BL/6小鼠的IFN-γ水平高于BALB/c小鼠,而IL-10水平低于BALB/c小鼠。这表明P.bANKA感染过程中,Tregs通过修饰炎性应答介导CM发生。
ITo investigate activation characteristic and correlation with disease progression of regulatory T cells (Tregs) during Plasmodium. berghei ANKA infection. C57BL/6 and BALB/c mice were infected by intraperitoneal injection of 1×106 P.berghei ANKA parasitized erythrocytes. Parasitemia of individual mice was monitored by the microscopic examination of blood smear stained with Giemsa. Spleen cell suspension was prepared from the mice sacrificed on days 0、3、5、8 post infection (p.i.). Applying flow cytometry to quatitatively analyze the numbers of Tregs in total spleen CD4+T cells dynamically. The levels of IFN-γ and IL-10 in spleen supernatants were measured by ELISA kits. C57BL/6 mice died with cerebral malaria (CM) between days 8 and 11 p.i., while BALB/c mice survived until weeks 3-4 after infection and died of anemia and overwhelming parasitemia. The absolute number of Tregs in the spleen started to elevate after infection with the peaks on day 3 p.i. in CM-susceptible C57BL/6 mice or CM-resistant BALB/c mice,and gradually reduced in the later infection from day 5 p.i. to day 8 p.i., C57BL/6 mice showed the most significant decline in the numbers of Tregs on day 8 p.i.. The numbers of Tregs in BALB/c mice were significantly higher than that in C57BL/6 mice during infection. IFN-γ and IL-10 in cultured splenocyte supernatants of two mouse strains began to increase after infection with peaks on day 5 p.i. and decline on day 8 p.i compared to the peak on day 5 p.i. The results indicated slight decline of IFN-γ and significant decline of IL-10 in C57BL/6 mice; significant decline of IFN-γ and slight decline of IL-10 in BALB/c mice on day 8 p.i.. IFN-γ in C57BL/6 mice were significantly higher than that in BALB/c mice. And the level of IL-10 in the former was lower than that in the latter. These results suggest that Tregs mediate the development of cerebral malaria by modification of inflammatory response.
郑伟、武静静、李莹、潘艳艳、刘军、曹雅明
基础医学生物科学研究方法、生物科学研究技术
伯氏疟原虫ANKA调节性T细胞脑型疟疾
Plasmodium berghei ANKAregsM
郑伟,武静静,李莹,潘艳艳,刘军,曹雅明.4+CD25+Foxp3+调节性T细胞在脑型疟疾发生中的作用研究[EB/OL].(2010-05-24)[2025-08-18].http://www.paper.edu.cn/releasepaper/content/201005-592.点此复制
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