Molecular biological approach to allergy disease medical treatment

目的：探讨哮喘患者外周血中CD25~+T细胞活化的调节功能及T细胞受体(TCR)刺激后的Ca~(2+)反应在哮喘发病中的作用。方法：采集昭和大学、藤冈医院和昭和大学门诊患者的血样。用荧光成像技术分析细胞内钙离子的反应。结果：非哮喘患者外周血中CD25+高表达的CD25+Tregs对TCR刺激无反应，导致细胞增殖和钙离子反应不足。但与非哮喘患者相比，哮喘患者外周血中CD25+高水平的CD4+Tregs对刺激有反应，其钙离子反应模式可分为两类，即1型和2型。1型细胞多数细胞钙反应正常，但与正常细胞相比，细胞增殖增强，调节功能减弱。结论：我们发现非哮喘患者CD25；高CD4+T细胞的钙反应受损，但TCR参与后，哮喘患者细胞内的钙反应增强。这些观察结果提示，哮喘患者CD25~+高T细胞亚群的异常可能参与了慢性呼吸道炎症的发生。

Objective : The aim of this study was to investigate whether the functions of the CD25^<high> CD4+Tregs including regulation of CD25^-T cells activation and the Ca^<2+> response to T cell receptor (TCR) stimulation as a marker of anergy are changed in asthma. Methods: Blood samples were collected from the outpatients of Showa University Fujigaoka Hospital and Showa University. Ca^<2+> response were analyzed with fluoroimaging technique. Proliferation was analyzed by flow cytometry.Results : The CD25^<high> CD4+ Tregs from non-asthmatics were unresponsive to TCR stimulation, resulting in paucity of proliferation and Ca^<2+> response. However, in contrast to non-asthmatics, the CD25^<high> CD4+ Tregs from asthmatics were responsive to the stimulation, and the Ca^<2+> response pattern could be classified into two groups, Type 1 and Type 2. Type 1 cells exhibited normal Ca^<2+> response in most of cells, and showed enforced proliferation and weaker regulatory functions compared to the normal ones. In contrast, Type 2 cells were responsive but had a slight increase in intra-cellular Ca^<2+>, and partially functioned as regulatory cells.Conclusion : We identified impaired Ca^<2+> responses in CD25^<high>CD4+ Tregs from non-asthmatics but increasing Ca^<2+> responses in the cells from asthmatics upon TCR engagement. These observations suggested that abnormalities of CD25^<high>CD4+ Tregs in asthmatics are implicated in the chronic inflammation in the airway.