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

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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