调节性T细胞修饰前炎症应答对小鼠脑型疟疾发生的影响

为探讨调节性T细胞（Tregs）对伯氏疟原虫感染所致鼠脑型疟发生和感染结局的影响机制，用伯氏疟原虫ANKA株分别感染对照组和抗CD25单克隆抗体注射组C57BL／6小鼠，计数红细胞感染率；感染前和感染后3、5、8天制备脾细胞悬液，流式细胞术检测脾Tregs百分含量；ELISA和Griess方法检测脾细胞培养上清IFN-γ、IL-10和NO水平。结果表明大多数C57BL／6鼠于感染后8—11天死于脑疟，抗CD25单克隆抗体注射组小鼠感染后3～4周死于贫血和过度原虫血症。对照组小鼠脾细胞培养上清IFN-γ、NO、IL—10水平于感染后开始升高，感染后5天达到峰值，感染后8天与感染后5天相比，IFN-γ、NO轻微下降，IL-10显著下降。感染后3、5天，实验组IFN-γ、NO水平显著高于对照组，IL—10水平显著低于对照组。感染后8天，实验组和对照组IFN-γ、NO、IL-10水平得到逆转。这表明Tregs通过修饰前炎症应答影响伯氏疟原虫感染鼠脑型疟发生和感染结局。

The Influence of CD4+CD25+Foxp3+ Regulatory T Cells on the Cerebral Malaria of Mice Infected with Plasmodium berghei ANKA by Modification of Pro-inflammatory Response

To investigate the relative mechanism of regulatory T cells （Tregs） influencing the cerebral malaria development and infective outcome of mice infected with Plasmodium berghei ANKA （P. b ANKA）, 1 × 10^6 P. berghei ANKA parasitized erythrocytes were injected introperitoneally to infect C57BL/6 mice injected with anti-CD25 mAb and the control mice. The ratio of the infected RBC was counted. Mice were sacrificed to collect the spleen cells on days 0, 3, 5, 8 post infection （p. i. ）. The percentage of Tregs in total spleen CD4^＋ T cells was measured by flow cytometry. The levels of cytokines （IFN-γ and IL-10） and NO in splenocytes supernatants were assayed by ELISA and Griess reaction, respectively. P. berghei-infected mice depleted of Tregs by mAb treatment had significantly extended their survival time （3-4 weeks after infection） compared with infected controls treated with rat immunoglobulin M （8-11 days after infection）. Moreover, the infected control mice died of cerebral malaria when parasitemia was 15% - 20% , while Treg-depleted mice died of anemia and overwhelming parasitemia （70% -80% ）. For infected control mice, the level of IFN-γ, NO and IL-10 began to increase after infection with peaks on day 5 p. i. then decrease on day 8 p. i. , moreover the decline was slight for IFN-,/ and NO but significant for IL-10. For Treg-depleted mice, the levels of IFN-γ and NO also increased after infection with peaks on day 5 p. i. , higher than that in infected control mice, then deceased significantly on day 8 p. i. , lower than that in infected control mice. Interestingly, the IL-10 level of Treg-depleted mice was significantly lower than that in the infected control for day 3 and 5 p. i and increased markly on day 8 p. i. Its level was significantly higher than that in control mice. These results suggest that Tregs influence the cerebral malaria development and outcome of mice infected with Plasmodium berghei ANKA by modification of pro-inflammatory response.