Analysis of Pathogenesis of lichenoid tissue reactions

我们之前建立了一个小鼠模型，在该模型中，通过结肠移植CD4^+自身反应性克隆T细胞来实验性地诱导LTR。使用这个动物模型，可以从本项目中的观察中得出以下结论。某些自身反应性或allo-I-A反应性克隆的T细胞在体内已被证明是亲表皮的，但不是其他T细胞，在体外显示出向表皮的定向迁移。对细胞系和重组细胞因子的研究表明，角质形成细胞衍生的因子负责T细胞的趋皮性迁移。我们进一步研究了体内注射抗I-A、抗CD4和抗LFA-1单抗(MAb)对嗜表皮性T细胞局部转移引起的LTR和迟发型超敏反应(DTH)的影响。局部应用抗CD4或抗LFA-1单抗可预防LTR，但抗I-A单抗不能，所有单抗均可同样抑制DTH反应。抗LFA-1单抗也能抑制亲表皮游走，而抗I-A和抗CD4mAb则无此作用。这些结果表明，T细胞迁移到表皮的能力可能部分取决于其表面LFA-1.3的表达。为了探讨T细胞表面的哪些分子对T细胞的趋皮性迁移起作用，对不同克隆的T细胞进行了CD3、CD4、CD8、CD2、Mac-1和LFA-1的表达检测。流式细胞仪分析结果显示，LFA-1优先表达于亲表皮性T细胞表面。T细胞上LFA-1的存在是必要的，但不足以使T细胞能够迁移到表皮中，而且LFA-1的上调既不是必要的，也不足以成为亲表皮的。

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.