Der p2重组BCG诱导适应性CD4+CD25+ Treg产生并下调小鼠变应性气道炎症反应

目的： 卡介苗（BCG）是广泛应用的Th1应答诱导疫苗。近年来的几项研究认为分支杆菌疫苗可作为免疫佐剂诱导生成调节性T细胞并抑制哮喘气道炎症。我们前期构建了胞壁表达屋尘螨抗原Der p2的重组BCG疫苗（Der p2 rBCG）。本研究的目的是阐明Der p2 rBCG的免疫调节机制。方法：小鼠分别给予生理盐水、BCG、Der p2 rBCG免疫后，观察脾细胞中相关调节性T细胞亚群的相对比例和绝对数量。体外及在体观察Der p2 rBCG诱导产生的CD4+CD25+ Treg的抑制功能。结果：(1)Der p2 rBCG可以诱导CD4+CD25+ Treg的产生；(2)Der p2 rBCG诱导产生的CD4+CD25+ T细胞可以在体外以变应原特异的方式抑制效应CD4+T细胞的增殖；(3)Der p2 rBCG诱导产生的CD4+CD25+ T细胞可以在体内下调Der p2诱导的小鼠变应性气道炎症。结论：Der p2 rBCG可以诱导适应性CD4+CD25+ Treg的产生，并通过其介导的免疫抑制作用下调小鼠变应性气道炎症反应。

Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCG-induced adaptive CD4+CD25+ Treg

AIM: The bacillus calmette-guerin (BCG) vaccine is the most widely used Th1-inducing vaccine. In recent years, some studies argued that mycobacterium vaccae can be used as adjuvant to induce regulatory T cells (Treg) and then suppress asthmatic airway inflammation. We previously have engineered recombined BCG that expressed Der p2 of house dust mites (Der p2 rBCG) on the cell wall. The aim of this study is to investigate the immune regulatory mechanisms of Der p2 rBCG. METHODS: Mice were vaccined with PS, BCG or rBCG. The relative proportion and the absolute numbers of related Tregs in spleen cells were analyzed. The suppressive activity of Der p2 rBCG-induced CD4+CD25+ T cells was detected both in vitro and in vivo. RESULTS: (1) Der p2 rBCG induced a CD4+CD25+Foxp3+ T cell subtype. (2) Der p2 rBCG-induced CD4+CD25+ T cells suppressed the proliferation of Th2 effector cells in vitro in an antigen-specific way. (3) Der p2 rBCG-induced CD4+CD25+ T cells mediated Der p2 specific suppression of airway allergy in vivo. CONCLUSION: Der p2 rBCG induces a CD4+CD25+Foxp3+ T cell subtype, which suppresses inflammation in allergic airway in a mouse model.