| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Murine epiermis conatins Langerhans cells(LC)and Thy-1+ dendritic epidermal T cells(DETC). In this report, 1)The mechanism of activation of LC and DETC in transgenic mice, 2)the ontogeny of DETC and thy-1+ dermal dendritic cells(DC), and 3)the effects of MCSF on LC activation were examined. 1)Transgenic(tg)mice were generated using construct containing a 2.1 Kb segment containing the promoter sequences of human K14 gene, as well as a cDNA encoding MCP-1. A dramatic increase in number of I-Aq positive cells was observed and an increase in the number of such cells in the dermis had Birbech granules. Enhanced contact hypersensitivity responses were observed in MCP-1tg mice, and a significant increase of the number of DETC was observed, when croton oil were applied as a sensitizer in MCP-1 tg mice., There was little enhancement of B7-1 and B7-2 on LC of MCP-1 tg mice compared with wt mice. These data indicate that efficiently activating mechanism in DC and DETC may exist in K14/MCP-1 mice, . and that MCP-1 may be important for the regulation of immunological function in skin.
2)The ontogeny of DETC and thy-1+ dermal DC was examined using wt mice. DETC were already observed in day 16 embryo, and the number of gammadeltaTCR+ DETC increased gradually. The number of fetal thy-1+ dermal DC decreased gradually after day 16 embryo.
3)The effects of cytokines on the costimualtory molecules in purified LC were examined. M-CSF significantly upregulared B7-1 and B7-2 expressions on purified LC by 12 hours culture.
These data indicate that chemiokines like MCP-1 can influence the migration of LC and DETC,resulting in the modulation of cutaneous immune responses. The result concerning MCP-1 and M-CSF stronfgly suggests that LC and macrophages have some interaction during their differentiation processes.
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