| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
We previously established a mouse model in which the LTR was experimentally induced by colal transfer of CD4^+ autoreactive cloned T cells. Using this animal model, the following conclusions can be drawn from the observation made in this project.
1. Certain autoreactive or allo-I-A reactive cloned T cells that have been proven to be epidermotropic in vivo, but not other T cells, show directional migration toward the epidermis in vitro. Studies with cell lines and recombinant cytokines indicate that keratinocyte-derived factors are responsible for the epidermotropic migration of the T cells.
2. We further investigated the effects of in vivo administration of anti-I-A, anti-CD4 and anti-LFA-1 monoclonal antibodies (mAb) on the development of LTR and delayed-type hypersensitivity (DTH) responses evoked by local transfer of the epidermotropic T cells. Prevention of the LTR was achieved with local abministration of either anti-CD4 or anti-LFA-1 mAb, but not with anti-I-A mAb, while the DTH responses were equally inhibited by all the mAb. Anti-LFA-1 mAb also inhibited the in vitro epidermotropic migration, whereas anti-I-A and anti-CD4 mAb were inactive. These results indicate that the ability of the T cells to migrate into the epidermis may depend in part on their surface expression of LFA-1.
3. To incestigate which molecules on the T cells are responsible for epidermotropic migration of the T cells, various cloned T cells were tested for their expression of CD3, CD4, CD8, CD2, Mac-1 and LFA-1. The results of flow cytometric analysis showed that LFA-1 was preferentially expressed on the surface of epidermotropic T cells. The presence of LFA-1 on T cells was necessary, but not sufficient to render the T cells-capable of migrating into the epidermis and that up-regulation of the LFA-1 was neither necessary nor sufficient to become epidermotropic.
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