Molecular biological approach to allergy disease medical treatment

过敏性疾病医学治疗的分子生物学方法

• 批准号: 15591065
• 负责人: TOBE Takashi
• 金额: $ 2.24万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591065/
• 关键词: CD25^<high>CD4+Tregs; asthma; Ca^<2+> responses; anergy; CD45RO^+ T細胞; Ca^<2+>不応答性; anergy; CD25^<high>CD4^+CD45RO^+T細胞; Treg; Ca流入; 喘息; アレルギー反応; 不応答(anergy); CD25^<high>Treg

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.

目的：探讨哮喘患者外周血中CD 25 ^<high>CD 4 + T细胞的功能，包括调节CD 25 ^-T细胞活化和T细胞受体（TCR）激活后的Ca^&lt;2+&gt;反应（作为无反应性的标志）是否发生改变。方法：收集昭和大学附属富士丘医院和昭和大学附属富士丘医院门诊患者的血样。用荧光成像技术分析Ca^2+反应。结果：非哮喘患者的CD 25、<high>CD 4 + T细胞对TCR刺激无反应，导致细胞增殖和Ca^2+反应减少。然而，与非哮喘患者相比，哮喘患者的CD 25、<high>CD 4 + T细胞对刺激有反应，并且Ca^&lt;2+&gt;反应模式可分为两种类型，1型和2型。与正常细胞相比，1型细胞在大多数细胞中表现出正常的Ca^&lt;2+&gt;反应，并且表现出增强的增殖和较弱的调节功能。相反，2型细胞有反应性，但细胞内Ca^&lt;2+&gt;略有增加，部分起调节细胞的作用。结论：我们发现非哮喘患者的CD 25、CD 4 + T细胞的Ca^&lt;2+&gt;反应受损<high>，而哮喘患者的细胞在TCR结合时Ca^&lt;2+&gt;反应增加。提示哮喘患者CD_（25）、CD_（<high>4+）T细胞亚群的异常与气道慢性炎症有关。