Induction and regulation of Protective immune responses against malaria parasites

1.疟原虫对T细胞免疫应答的调节我们研究了约氏疟原虫17 XNL感染后恢复的小鼠的免疫应答和CD 4 ^+ T细胞的保护作用。从疟疾感染恢复的小鼠脾脏中提取的CD 4 ^+ T细胞显示出特异性增殖反应。然而，它们产生有限水平的IL-2和高水平的IL-10。这些纯化的CD 4 ^+ T细胞的连续转移不能产生对抗子孢子感染的保护性免疫。这些结果表明，疟原虫感染小鼠的CD 4 ^+ T细胞在功能上受到调节。2.树突状细胞在疟疾感染小鼠中的功能我们表征了约氏疟原虫感染小鼠树突状细胞的功能。与正常树突状细胞相比，响应于Toll样受体刺激的IL-12的产生减少，而IL-10的产生增加。活化抗原特异性T细胞的能力在MHC I类和II类途径中均未降低。我们将继续研究这些树突状细胞激活的T细胞增加IL-10产生和功能的分子机制。3.树突状细胞和巨噬细胞中调节免疫应答的转录因子IRF-4的功能转录因子IRF-4在免疫细胞包括淋巴细胞、树突状细胞和巨噬细胞中表达。我们已经发现，IRF-4在树突状细胞亚群的分化中起着关键作用，并对TLR介导的信号传导具有抑制作用。这种抑制主要调节MAP激酶JNK和NF-κB的活化。

1.Modulation of T-cell immune responses by malaria parasitesWe studied immune responses and the protective effect of CD4^+ T-cells in mice recovered from P.yoelii 17XNL infection. CD4^+ T-cells from spleen of mice recovered from malaria infection showed spesific proliferative responses. However, they produced limited levels of IL-2 and high levels of IL-10. Adoptive transfer of these purified CD4^+ T-cells could not confer protective immunity against sporozoite infection. These results suggested that CD4^+ T-cells in Plasmodium-infected mice are functionally modulated.2.Function of dendritic cells in malaria-infected miceWe characterized function of dendritic cells from mice infected with P.yoelii. Production of IL-12 in response to Toll-like receptor stimulation was reduced when compared with normal dendritic cells while IL-10 production was augmented. The ability to activate antigen specific T-cells was not reduced in both MHC class I and class II pathways. We will continue to study molecular mechanisms underlying augmented IL-10 production and function of T-cells activated by these dendritic cells.3.Function of IRF-4, transcription factor that regulates immune responses, in dendritic cells and macrophagesTranscription factor IRF-4 is expressed in immune cells including lymphocytes, dendritic cells and macrophages. We have revealed that IRF-4 plays a critical role for the differentiation of a subset of dendritic cells and has inhibitory role for the TLR-mediated signaling. This inhibition mainly regulates activation of MAP kinase JNK and NF-κB.