Molecular mechanism for homing of T cells to the epidermis

T细胞归巢至表皮的分子机制

基本信息

批准号：
04454288
负责人：
SHIOHARA Tetsuo
金额：
$ 4.35万
依托单位：
Kyorin University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454288/
关键词：
Dendritic epidermal cells (dEC)T cell receptor (TCR)alphabeta Bone marrow cells Fixed drug eruption (FDE)TCRTCR Valpha-Vbeta gene usage RT-PCR CLA Adhesion molecules TCR Valpha・Vbeta遺伝子表皮内T細胞 LFA-1 自己反応性T細胞 GvH病 αβ型T細胞レセプター

项目摘要

Although earlier studies suggested that in mice homing of T cells to the epidermis is a unique property of Vgamma5^+ fetal thymocytes, we demonstrated that adult bone marrow (BM) cells migrate into the epidermis and differentiate there into T cell receptor (TCR)-alphabeta^+ CD8^+ dendritic epidermal cells (dEC), a phenotype not previously demonstrated in dEC.We further demonstrated that adult thymocytes also migrate to the epidermis and give rise to TCR-alphabeta^+ CD8^+ dEC.However, our failure to analyze TCR repertoire of these TCR-alphabeta^+ CD8^+ dEC by RT-PCR method prevented us from determining whether expression of particular TCR could be required for the homing of these T cells to the epidermis.We next took an alternative approach, Based on the previous suggestion that disease with selective destruction of epethelia may be mediated by T cells indigenously residing in epithelial tissue, such as dEC : In this regard, fixed drug eruption (FDE) appeared to have unique features best suited for analyzes of epidermal T cells ; T cells were prepared from the lesional epidermis in patients with FDE a long period after clinical resolution and their TCR repertoire and expression of adhesion molecules were examined. Comparative analyzes of TCR Valpha and Vbeta expression in the epidermal T cells and the paired PBL by quantitative RT-PCR demonstrated that TCR Valpha and Vbeta gene usage of the epidermal T cells is very restricted and that the restriction is much more apparent in those isolated from the lesion after multiple episodes. These results indicate that epidermal homing of the T cells may not be determined by particular TCR specificities but expansion of epideermal T cells with particular TCR would occur in situ after multiple episodes. Because these epidermal T cells have the much higher LFA-1 and CLA levels as compared with PBL, the high level expression of these molecules may be determinative of epidermal homing of certain T cells.

尽管早期的研究表明，在小鼠中，T 细胞归巢到表皮是 Vgamma5^+ 胎儿胸腺细胞的独特特性，但我们证明，成体骨髓 (BM) 细胞迁移到表皮并在那里分化为 T 细胞受体 (TCR)- Alphabeta^+ CD8^+ 树突表皮细胞 (dEC)，这是以前在 dEC 中未证实的表型。我们进一步证明，成年胸腺细胞也迁移到表皮并产生 TCR-alphabeta^+ CD8^+ dEC。然而，我们未能通过 RT-PCR 方法分析这些 TCR-alphabeta^+ CD8^+ dEC 的 TCR 库，这使我们无法确定是否需要特定 TCR 的表达为了使这些 T 细胞归巢到表皮。我们接下来采取了另一种方法，基于之前的建议，即选择性破坏上皮细胞的疾病可能是由固有地驻留在上皮细胞中的 T 细胞介导的组织，例如 dEC：在这方面，固定药疹 (FDE) 似乎具有最适合分析表皮 T 细胞的独特特征；在临床缓解后很长一段时间内，从 FDE 患者的病变表皮中制备 T 细胞，并检查其 TCR 库和粘附分子的表达。通过定量 RT-PCR 对表皮 T 细胞和配对 PBL 中的 TCR Valpha 和 Vbeta 表达进行比较分析表明，表皮 T 细胞的 TCR Valpha 和 Vbeta 基因使用非常有限，并且这种限制在从多次发作后的病变。这些结果表明，T细胞的表皮归巢可能不是由特定TCR特异性决定的，但具有特定TCR的表皮T细胞在多次发作后会在原位发生扩增。由于与 PBL 相比，这些表皮 T 细胞具有更高的 LFA-1 和 CLA 水平，因此这些分子的高水平表达可能决定某些 T 细胞的表皮归巢。