Molecular mechanism for homing of T cells to the epidermis

点击翻译按钮获取中文摘要

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.