| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
Both CD4^+ and CD8^+T lymphocytes in the mesenteric lymph node (MLN) proliferated markedly 2 weeks after infection with Nippostrongylus brasiliensis (Nb) in rats or 7 to 10 days after infection in mice, when MLN swelling reached the maximum. After infection, CD4^+ showed high levels of IL-3, IL-4, IL-5, and IL-13 gene expression, which was scarcely detected before infection. In CD8^+, IL-3, IL-5, and IL-13 mRNAs increased greatly, but IL-4 mRNA was not detected at all after infection. IL-10 mRNA was strongly enhanced in CD8^+ after infection, while detected at high levels before and after infection in CD4^+. An ELISPOT assay also showed that there were few if any CD8^+T cells which actually produced IL-4 in murine MLN after infection, while many CD4^+T cells produced this cytokine. The excretory-secretory antigens (ES) obtained from adult worms suppressed the productivity of IFN-γ in both CD4^+ and CD8^+T cells in a dose-dependent manner. This seemed to be a direct effect of ES to lymp
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hocytes without involving the activation in type2 cytokines, because it did not affect IL-4 production from CD4^+ and that of IL-10 from both CD4^+ and CD8^+. The results that only IL-4 mRNA in type2 cytokines was not detected in CD8^+ after infection despite of suppression in IFN-γ production may suggest that there are some mechanisms in which IL-4 gene expression is specifically inhibited in CD8^+. To investigate the roles of CD8^+T cells, histological changes in the intestine and changes in levels of cytokine gene expression in the MLN were compared between normal mice and anti-CD8 antibody-injected mice or CD8-deficient mice after Nb infection. The pathological changes peaked at day 7 after infection, which showed mild inflammation in propria mucosa and submucosa, and the severity of histological changes and the repairing process were similar in both groups. The gene expression in cytokines such as IL-4, Il-10, IL-13, and IFN-γ did not show significant differences between them. Taken together, it has been revealed that both CD4^+ and CD8^+T cells greatly increase in MLN after Nb infection, but the pattern of cytokine gene expression in CD8^+ is different from that in CD4^+. It was suggested, however, that CD8^+T cells were not largely involved in the development of histological changes and repairing process or in the induction of cytokine milieu in the nematode infection. Less
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