A study on involvement of cytokines in immune response to parasite infections using immune response-reacted gene defective mice

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Cytokines play a variety of crucial regulatory roles in the host response to parasites. To analyze complecated immune responses in parasite infections, we investigated effects of IFN-gamma and IL-4 on parasite infections by using IFN-gamma receptor and IL-4 gene knockout mice (IFN-gamma R^% and IL-4^%, respectively), wild type C57BL/6 mice, resistant to L.major, and wild type BALB/c micc, suceptible to this organism. The obtained results are as follows. 1.IL-4^% and C57BL/6 mice showed a weak footpad swelling, when these mice were infected s.c.with L.major. On the other hand, high intensity of footpad swelling was observed in IFN-gamma R^% and BALB/c mice infected with L.major. 2.The number of IFN-gamma or IL-4 producing cells were measured in the popliteal lymphnodes, the spleen, and the liver of BALB/c and C57BL/6 mice using enzyme-linked immunospot assay and flow cytometry. The reaction as follows. (1) IFN-gamma Producing cells were detected in the presence of L.major antigens in BALB/c and C57BL/6 mice, and the number of the IFN-gamma Producing cells in C57BL/6 mice was more than that in BALB/c mice. (2) The IFN-gamma producing cells could not be detected in vitro in the abscence of the antigens in both mice by 5 weeks post infection. (3) IL-4 producing cells were detected from the spleen and the liver of BALB/c mice and increased with the progress of the infection. (4) Phenotype of IL-4 producing cells in the liver of BALB/c mice were gammadelta^+T cells, alphabeta^+T cells, and CD4^-CD8^- cells. gammadelta^+T cells incrcased at 2 week post infection and alphabeta^+T cells incrcased at 4 week. CD4^-CD8^- cells produced IL-4 during only early phase of the infection. Studies to analyze these phenomena are currently underway.