A Study of Autoreactive T Cells in Drug-Induced Autoimmune Skin Disease

1)从临床组织病理学上看，药疹属于急性皮肤移植物-疱疹-宿主病亚群，我们观察到表皮CD8+ T细胞浸润为主，CD1+表皮朗格汉斯细胞耗损/减少，角化细胞上HLA-DR/ICAM-1表达显著。这些发现与骨髓移植和输血后出现的急性皮肤GVHD本身相同，表明这两种情况的病理机制基本相同，并且具有细胞毒性活性的T细胞和IFNgamma、TNFalpha等炎症细胞因子的增强可能在药物作用下GVHD本身和GVHD样反应的发展中起重要作用。2)在巯基药物局部转移的足垫反应中，tiopronin （TP）致敏的淋巴结细胞（LC）和脾脏细胞（SC）、IFNgamma和TNFalpha也需要充分诱导gvhd样反应。3)我们已经通过流式细胞术发现，活化T细胞释放的IFNgamma可增强大疱性类天疱疮（BP）抗原在培养的角化细胞上的表达。在本研究中，我们发现BP抗原在信使RNA水平上的表达增强。这些结果再次证实，来自活化T细胞的ifnγ等细胞因子可能参与自身免疫性大疱性类天疱疮的发展。

1) In the drug eruptions, which were classified to the subgroup of acute cutaneous GVHD (graft-verusus-host disease) type from the clinicohistopathological findings, we observed the dominant infiltration of CD8+ T cells in the epidermis, depletion/reduction of CD1+ epidermal Langerhans cells and remarkable expression of HLA-DR/ICAM-1 on the kerationcytes. These findings are the same as acute cutaneous GVHD itself appeared after bone marrow transplantation and blood transfusion, indicating that essentially the same pathomechanism is involved in the both conditions, and also that enhancement of T cells with cytotoxic activity and the inflammatory cytokines such as IFNgamma and TNFalpha may play an important role in development of GVHD itself and GVHD-like reaction by drugs.2) In the footpad reactions by local transfer of sulfhydril drug, tiopronin (TP)-sensitized lymph node cells (LC) and spleen cells (SC), IFNgamma and TNFalpha were also required for the full induction of GVHD-like reactions.3) We have already revealed that IFNgamma, which is released from the activated T cells, enhances the expression of bullous pemphigoid (BP) antigen on the cultured keratinocytes by flow cytometory. In this study we revealed the enhanced expression of BP antigen in the messenger RNA levels by slot blot hybridization. These results reconfirmed the possibility that cytokines such as IFNgamma from the activated T cells might be involved in development of autoimmune bullous pemphigoid.