重症大疱型药疹是皮肤科的危重疾病。CD8+T细胞和角质形成细胞在其发病机制中均有重要作用，但二者的相互关系尚不完全清楚。前期实验发现TNF-α和CCL27在患者外周血和皮损局部均升高。TNF-α由活化的CD8+T细胞分泌，可促进CCL27的分泌；而CCL27由角质形成细胞产生，并参与CD8+T细胞活化。由此我们提出假说，在重症大疱型药疹中，CD8+T细胞分泌的TNF-α刺激角质形成细胞分泌CCL27，而CCL27促进CD8+T细胞分泌TNF-α。两种细胞通过“细胞因子桥梁”，形成“环路扩大效应”。本研究拟通过分离CD8+T细胞和角质形成细胞，运用慢病毒包装与感染、ELISA、Western blot、Real-time PCR、免疫荧光等技术手段，结合transwell细胞共培养体系，探索CD8+T细胞和角质形成细胞在重症大疱型药疹中的互调作用，为深究疾病的发病机制和临床防治提供依据。

Severe bullous drug eruption (SBDE) is a lethal dermatological disease. CD8+ T lymphocytes and keratinocytes are considered to play an important role in the pathogenesis. However, the inter-regulation between the two cells is not clear yet. Our previous studies have found that TNF-α and CCL27 in the peripheral blood and the skin lesions of patients with SBDE were increased. TNF-α is secreted by activated CD8+ T cells and can stimulate secreation of CCL27. CCL27 is generated by keratinocytes and is involved in the activation of CD8+ T cells. Therefore, we raise the hypothesis that in the pathogenesis of SBDE, TNF-α secreted by the CD8+ T cells can stimulate keratinopcyte to produce CCL27, whereas, CCL27 promote CD8+ T cells to generate TNF-α. The two cells are linked through the “cytokine bridge”, which cause the “positive loop effect”. In this study, we will isolate CD8+ T cells and primary keratinocytes from the patients with SBDE, and use the techniques including lentivirus packaging, ELISA, Western blot, Real-time PCR, immunofluorescence and cell co-culture system of transwell, in order to study the key link between CD8+ T cells and keratinocytes in SBDE. The results will be beneficial to the pathogenesis and can provide theoretical and experimental basis to the clinical prevention and treatment of the disorder.