Role of alphaEbeta7 on tissue destruction of autoimmune diseases

为了表征激活的PBL及其在SLE发病机制中的作用，我们开发了一系列针对SLE PBL表面结构的单克隆抗体。我们重点研究了一种名为SM-17的单克隆抗体，它能在CD8+T细胞上与活化抗原反应。免疫沉淀分析清楚地表明SM-17识别的抗原为α ^Ebeta_7 (cd103)，这是首次在上皮内淋巴细胞上鉴定到的表面抗原。检测了α ^Ebeta_7 （cd103）在多种自身免疫和血液病患者有或没有PHA刺激时的表达。我们发现alpha^Ebeta_7 （cd103）的表达在系统性红斑狼疮患者和1例毛细胞白血病患者在没有刺激的情况下显著升高。不仅CD8+ T细胞表达增强，SLE患者的CD4+ T细胞也表达增强。cd103的表达增强与口腔溃疡或浆液炎的存在显著相关，提示其可能涉及这些部位的组织损伤。对HSG上皮细胞系的黏附实验表明，cd103表达增强的T细胞对HSG有较强的黏附，可被抗α ^Ebeta_7抗体部分阻断。这些结果表明这种新型整合蛋白在组织损伤中的作用，特别是上皮细胞，上皮细胞表达E-cadherin， cd103的高表达。

To characterize the activated PBL and the role on pathogenesis in SLE, we have developed a series of monoclonal antibodies directed against the surface structures on the SLE PBL.We focused on the one monoclonal antibody designated SM-17, which reacted to the activation antigen on CD8+T cells. immunoprecipitation analysis clearly showed that the antigen recognized by SM-17 was alpha^Ebeta_7 (CD 103), which was first identified the surface antigen on the intra-epithelial lymphocytes. The expression of alpha^Ebeta_7 (CD 103) was examined in the a variety of autoimmtme and hematological patients with or without stimulation of PHA.We found that the expression of alpha^Ebeta_7 (CD 103) was significantly elevated in patients with SLE after stimulation with PHA, and one patient with hairy cell leukemia in the absence of stimulation. The enhanced expression was not only observed in CD8+ T cells, but also in CD4+ T cells from SLE patients. Th enhanced expression of CD 103 is significantly correlated with the presence of oral ulcers or serositis, suggesting that it may involve in tissue injury in these sites. Adhesion experiments against the HSG epithelial cell lines showed that the T cells with enhanced expression of CD 103 strongly adhered onto HSG, which was partially blocked by anti-alpha^Ebeta_7 antibody. These results suggest a role of this novel inte grin on the tissue injury, particularly epithelial cells, which are expressing E-cadherin, a higand for CD 103.