| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
1.Contact hypersensitivity (CHS) is a T-cell-mediated skin inflammatory response. It is controversial whether CD4(+) T cells play an enhancing or regulatory role in the pathogenesis of CHS. Because interleukin (IL)-16 is a chemoattractant cytokine for CD4-expressing cells, we investigated the involvement of IL-16 in the CHS reaction. IL-16 production was induced in the epidermis and dermis during the elicitation phase of the CHS response with trinitrochlorobenzene. In the sensitization phase, the single application of haptens such as trinitrochlorobenzene and oxazolone also induced IL-16, whereas primary irritants or vehicle control did not. IL-16 was produced mainly by CD11c-negative cells in the epidermis during the elicitation phase. Furthermore, treatment of sensitized mice with anti-IL-16 neutralizing MoAb enhanced the ear swelling and reduced the number of infiltrating CD4(+) T cells. These data indicate that IL-16 plays a role in CHS, whereby IL-16 induces CD4(+) T cells and the
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se CD4(+) T cells subsequently exhibit down-regulating properties.
2.Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of histamine, and the phenotypes and function of these cells were analyzed. Histamine induced the generation of CD1a-CD14+ cells, which exhibited cytological and phenotypical characteristics of dendritic cells (DC), showed enhanced phagocytic activity and cytokine-producing capacity, but demonstrated weak allo-stimulatory capacity compared with CD1a+CD14- MoDC. The inhibitory effects of histamine on CD1a+CD14- MoDC differentiation were antagonized by cimetidine, an H2 receptor antagonist, but not by H 1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. Culture supernatant of histamine-treated monocytes also inhibited CD1a+CD14- MoDC differentiation, which was restored by the removal of IL-10. These results suggest that histamine-driven CD1a-CD14+ DC regulate inflammatory reaction, and thereby may be used for induce tolerance in atopic disorder. Less
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