Analysis of TH1/TH2 imbalance in Shogren's syndrome and its strategic control

本课题旨在分析TH1/TH2失衡及其在干燥综合征发病机制中的作用，特别是从病变部位局部T细胞免疫应答的角度进行分析我们从干燥综合征患者的唇活检获得的小唾液腺中分离出涎腺浸润T淋巴细胞，并进行特征性TH1或TH2细胞因子谱的检查。抗cd3抗体刺激后细胞因子的体外生成试验以及从唾液组织分离的细胞的细胞因子分析表明，在Shogren综合征中，T细胞浸润以TH1为主。对从唾液腺中建立的许多T细胞克隆的进一步分析显示TH1细胞在组织中积累。对患者外周血T细胞的类似研究表明，该疾病患者存在全身免疫偏差以及病灶局部TH1优势2我们试图找到一种策略来控制我们在这种疾病中发现的免疫偏差。几种化合物和细胞因子的体外施用表明，即使在体内系统中也可能恢复TH1/TH2平衡。本研究将为分析与免疫病理抗原相关的自身免疫性疾病中TH1/TH2平衡和免疫偏差提供有益的应用。

This research project was aimed to analyze the TH1/TH2 imbalance and its role in the pathogenesis of Sjogren syndrome especially from the point of view of the local T cell immune responses at the lesion.1 We have isolated salivary glands-infiltrating T lymphocytes from minor salivary glands obtained by lip biopsy from the patients with Sjogren syndrome, and rendered to the examination for the characteristic TH1 or TH2 cytokine profile. The in vitro production assay of cytokines after stimulation with anti-CD3 antibodies as well as the intracellular cytokine analysis of the cells isolated from the salivary tissue demonstrated the TH1 predominance of the T cell infiltrates in Shogren's syndrome. Further analysis of the many T cell clones established from the salivary glands revealed the TH1 cells accumulation in the tissue. Similar studies with peripheral blood T cells from the patients indicated that the individuales with the disease have systemic immune deviation as well as the local TH1 predominance in the lesion.2 We attempted to find a way of strategic control of the immune deviation we found in the disease. In vitro administration of several compounds and cytokines showed the possible restoration of TH1/TH2 balance may be obtained even in the in vivo system.The approach we used in this study will provide a useful application to the analysis of TH1/TH2 balance and the immune deviation in the autoimmune diseases which are associated with immunopathological antigens most of that have not identified yet.