HBV转基因小鼠免疫耐受状态的研究

A study on immune tolerance state in HBV transgenic mice

目的研究HBV转基因小鼠免疫耐受状态机制。方法以正常ICR小鼠为对照,检测转基因小鼠脾树突状细胞(DC)表面la(MHC-Ⅱ)和CD_(80)(B7)表达水平及其免疫功能;脾及外周血T淋巴细胞表面CD_8和CD_(28)及肝细胞膜上MHC-I和腹腔巨噬细胞MHC-Ⅱ抗原表达情况。结果发现HBV转基因小鼠DC表面MHC-Ⅱ及CD_(80)表达水平(13.34±1.11及12.24±1.31)明显低于对照组(20.47±1.78及15.83±1.52,P<0.05);其DC体外诱发T淋巴细胞增殖能力(6409.67±445.71cpm)明显低于对照组(13870.67±1706.9cpm,P<0.01);而脾及外周血T淋巴细胞CD_8及CD_(28)表达水平与对照组差异不明显;肝组织冰冻切片免疫组化测定其MHC-Ⅰ抗原表达量低于正常对照组;腹腔巨噬细胞表面 MHC-Ⅱ抗原表达水平明显低于正常对照组。结论本研究表明 HBVH基因小鼠免疫耐受状态并非免疫系统单一环节障碍,在抗原提呈细胞、靶细胞抗原标志,特异性细胞免疫应答等方面均存在免疫功能低下及调节、识别障碍,其中DC功能低下,在免疫耐受状态中有重要作用。

To study immune tolerance mechanism of HBV transgenic mice (HBV-Tg). Methods The expression levels of MHC- Ⅱ , CD80 on DC and CD8, CD28 on T lymphocytes of spleen and peripheral blood as well as MHC- I on hepatocytes were detected. Results The expression levels of MHC- Ⅱ and CD80 were significantly lower on DC from HBV-Tg than on that from controls (P<0.05). Furthermore, the ability to induce T lymphocyte proliferation was markedly lower for DC from HBV-Tg than that from controls. There was no significant difference in expression levels of CD8 and CD28 on T lymphocytes of spleen and peripheral blood between the two groups. Immunohistochemistry showed that the expression level of MHC- I antigens on hepatocytes from HBV-Tg was lower than that from controls. Conclusion The immune tolerance of HBV-Tg is closely related to the presenting function of APC, antigen marker on target cells and specific cell immune reaction. Among these factors, lower immune function of DC might be an important one for immune tolerance state of HBV-Tg.