Analysis of Mechanisms by Which T Cells Migrate to the Epidermis

我们先前在体外和体内都建立了具有特异性趋化表皮的小鼠T细胞克隆。使用这些T细胞克隆，我们试图阐明某些T细胞优先迁移到小脑的机制。为了确定哪些细胞粘附分子参与T细胞的表皮转移，通过流式细胞术分析检测了在表皮和非表皮T细胞克隆上的罕见T细胞表面分子的表达。结果表明，LFA-1优先表达于亲表皮T细胞克隆的表面，而非亲表皮T细胞克隆对LFA-1呈阴性或弱阳性。在琼脂凝胶下的体外迁移试验中，这些亲表皮性T细胞显示出向表皮的定向迁移。抗体抑制研究表明，在各种抗T细胞表面分子的mAb中，只有抗LEA-1 mAb完全抑制T细胞向表皮的体外迁移。这些发现表明LFA-1在引导T细胞向表皮迁移中也起着重要作用.结果发现，表皮结构自发地从由表皮内注射亲表皮T细胞诱导的破坏中恢复，变得对随后的T细胞诱导破坏的尝试具有抗性。这种抗性与Thy 1^+表皮细胞数量的大幅增加密切相关。在无胸腺裸鼠和切除胸腺的成年小鼠中未诱导出抵抗。胸腺内成熟的Thy 1^+ EC的扩增是诱导抗性的关键。

We previously established murine T cell clones with special tropism the epidermis both in vitro in vivo. Using these T cell clones, we attempted to elucidate the mechanisms by which certain T cells preferentially migrate to the epidemis.1. To determine which cell adhesion molecules are involved in epidermotrpoism of T cells, the expression of rariaus T-cell surface molecules on epidermotropic and non-epidermotropic T cell clones was examined by flow cytometric analysis. The results showed that LFA-1 was preferentially expressed on the surface of epidermotropic T cell clones, while non-epidermotropic T cell clones were negative or weakly positive for LFA-1.2. These epidermotropic T cells showed directional migration toward the epidermis in an in vitro migration assay under agar gel. Antibody inhibition studies demonstrated that of various mAb to T-cell surface molecules only anti-LEA-1 mAb completely inhibited the in vitro migartion of the T cells toward the epidermis. These findings indicate that the LFA-1 also plays an important role in directing T cell migration to the epidermis.3. It was found that epidermal structures that had spontaneously recovered from the destruction induced by inteademal injection of the epidermotropic T cells became resistant to subsequent attempts to induce the destruction by the T cells. This resistance correlated well with the great increase in Thy 1^+ epidermal cell numbers. The resistance was never induced in athymic nude mice and adult thymectomized mice. The expansion of the Thy 1^+ EC that mature in thymus would be crucial to the induction of the resistance.