鼠型衣原体活化的CD86+B细胞分泌IFN-γ抑制气道过敏反应的机制研究

It is very important to investigate the mechanism of microbial infection in inhibiting allergic responses, which is meaningful for prevention and treatment of allergic diseases. Researches have shown that Chlamydial muridarum lung infected could inhibit experimental airway allergic response. B cells is important antibody secretion resource and antigen presenting cell, which plays an integral role in inflammatory responses and allergic responses. In our previous researches, splenic B cells from chlamydial lung infected mice (Cm-B) showed an obvious inhibition on OVA induced airway allergic responses. Comparing to naïve B cells, Cm-B cells showed an increase in CD86 expression and an increased in secreting IFN-γ. Furthermore, IFN-γ secreted by Cm-B cells was proven play a vital role in inhibiting allergic response by using antibody for blocking IFN-γ. However, the inhibition effect of Cm-B cells on airway allergic response need to be confirmed. This program aims to explore and the impact of Cm infection on B cells, the changes of T cell and subpopulation responses following Cm-B adoptive transfer, as well as the direct or indirect effect of Cm-B cells on eosinophils’ infiltration in airway allergic responses, to explore the mechanism of Cm activated B cells inhibition on airway allergic responses. Human blood experiments were introduced to certify the investigation and the results may provide a new prospect in allergy precaution and treatment.

探究病原体感染对过敏的影响及机制在过敏的预防和治疗中具有重要意义，已有研究发现沙眼衣原体呼吸道感染可以抑制实验性气道过敏反应。B细胞是重要的抗体分泌细胞和抗原提呈细胞，在感染和过敏中发挥重要作用。本研究前期实验结果显示，鼠型衣原体呼吸道感染小鼠脾B细胞(Cm-B)对OVA诱发的气道过敏反应具有明显的抑制作用，且Cm-B较naïve B细胞CD86的表达增强、IFN-γ分泌增多；抗IFN-γ抗体封闭可以消除Cm-B对气道过敏反应的抑制作用，提示鼠型衣原体感染后通过Cm-B表达CD86及分泌IFN-γ实现抑制气道过敏反应。本课题拟通过研究鼠型衣原体感染对B细胞的影响、Cm-B过继转移对过敏小鼠T细胞及亚群变化，以及Cm-B对嗜酸性粒细胞迁移和凋亡的影响等，阐明Cm-B抑制气道过敏反应的机制。此外，还设计利用人外周血标本进行验证实验，所得研究成果可以为过敏反应治疗和预防提供新的思路。

本研究旨在通过探究衣原体感染小鼠脾B细胞对OVA诱发的气道过敏反应的抑制作用及机制，探索“卫生假说”现象及为青少年哮喘疾病的预防和治疗提供研究靶点和治疗方向。本项目实验结果显示，鼠型衣原体呼吸道感染小鼠脾B细胞(Cm-B)对OVA诱发的气道过敏反应具有明显的抑制作用，这种抑制作用是通过分泌低水平的IFN-γ即可以实现，封闭抗IFN-γ抗体可以消除Cm-B对气道过敏反应的抑制作用。这种抑制作用主要表现在抑制Th2反应、抑制嗜酸性粒细胞的浸润、抑制肺组织炎症反应、抑制过敏特异性免疫球蛋白的产生等。此外，解决了一个技术疑问，利用质谱流式技术验证了本模型中，B220磁珠阳性筛选富集的细胞含有B细胞纯度高，且较低水平的IFN-γ主要来自于B细胞而非T淋巴细胞。这一验证方法，为今后应用的可能提供技术支持。