Development of dendritic cells and functional regulation of host T cell responses in mice with concurrent multiple parasitic infections

探讨了多种寄生虫感染过程中Th1/Th2分化的免疫学机制。A/J小鼠对查鲍迪疟原虫(Pc)感染敏感，但同时感染曼氏血吸虫(Sm)的小鼠可能通过增加干扰素γ的产生而对疟疾产生抵抗力。这个假设是在伴随感染的小鼠期间树突状细胞(DC)和T细胞相互作用的功能变化。曼氏血吸虫可溶性虫卵抗原在体外不能激活A/J小鼠的DC，包括脾和髓系DC。比较合并感染和单独感染疟疾小鼠的DC表型，发现混合感染的A/J小鼠CD8和DC的频率均低于易感对照A/J小鼠。提示CD8~+树突状细胞可能参与了A/J小鼠抵抗Pc感染的机制。虽然在混合感染的小鼠中观察到干扰素γ的产生上调，但DC并没有表现出增加IL-12的产生。通过混合感染小鼠到未感染小鼠的细胞转移实验，检测DC的直接作用。到目前为止，在我们测试的细胞数量上，没有证据表明DC可以转移A/J小鼠对Pc的耐药性。另一方面，T细胞功能的多样性可能影响A/J小鼠对Pc的易感性。比较不同感染情况下A/J小鼠Treg细胞的诱导情况。Treg细胞的频率有明显差异。在对Pc耐药的混合感染小鼠中，与对照Pc感染相比，Treg细胞的频率更高。此外，用抗CD25单抗治疗的混合感染小鼠再次对Pc易感。综上所述，我们认为在曼氏血吸虫混合感染过程中对沙包氏杆菌的抗性似乎是由Treg细胞调节的，而树突状细胞的参与并不清楚。

Immunological mechanisms of Th1/Th2 dichotomy during multiple parasitic infection were investigated. A/J mice were susceptible to Plasmodium chabaudi (Pc) infection, however, mice concurrently infected with Schistosoma mansoni (Sm) became resistant to the malaria possibly through enhanced IFNγ production. The hypothesis was functional alterations in dendritic cells (DC)-T cells interaction during-the concomitant infected mice. DC, both splenic and myeloid, of A/J mice were not activated under the stimulation of soluble egg antigen of S.mansoni in vitro. When surface phenotypes of DC were compared between mice co-infected or malaria alone, frequency of CD8^+ DC were lower in the co-infected A/J mice than susceptible control A/J mice. This suggested that CD8^+ dendritic cells might be involved in resistant mechanism of A/J mice against Pc infection. Although upregulated IFNγ production was observed in co-infected mice, DC did not show enhanced IL-12 production. Direct effects of DC were tested by cell transfer experiments from co-infected mice to naive mice. So far at the cell number we tested, there was no evidence that DC can transfer the resistance of A/J mice against Pc. On the other hand, functional diversities of T cells could affect the susceptibility of A/J mice to Pc. Induction of Treg cells was compared among different infectious situation of A/J mice. Apparent difference was observed for the frequency of Treg cells. In the co-infected mice, which were resistant to Pc, showed higher frequency of Treg cells compared with control Pc infection. More over, co-infected mice treated with anti-CD25 mAb became susceptible to Pc again. Together, it was suggested that resistance to P.chabaudi during co-infection of S.mansoni seemed to be regulated by Treg cells, while involvement of dendritic cells was not clearly shown