两种单纯疱疹病毒载体在大鼠脑内所致免疫应答的比较

Comparison of the Immune Response to Gene Transfer into the Rat Brain with Helper or Helper Virus-free HSV-1 Vectors

目的 比较使用 p HSVlac/ helper或 p HSVlac/ helper virus- free两种载体包装系统进行基因转移时所引起的免疫应答。方法 分别将两种载体定位注射到大鼠纹状体内 ,采用免疫组化方法检测并计数包括TCR、CD4、CD8、MHC- 和 MHC- 在内的几种免疫反应阳性细胞。结果 两种载体包装系统引起的 TCR、CD4和 CD8免疫反应阳性细胞浸润高峰出现在基因转移后的第 7天 ,MHC- 和 MHC- 反应高峰在第 4天。它们对p HSVlac/ helper的反应明显大于对 p HSVlac/ helper virus- free的反应 (P<0 .0 0 1) ,前者是后者的 3～ 12倍 ,并且 ,p HSVlac/ helper virus- free所致的细胞浸润迅速消退接近 PBS对照组水平。

Objective This study was conducted to compare the immune response to gene transfer with helper virus or helper virus-free vectors. Methods Two vector stocks were delivered by stereotactic injection into the striatum and then the immune response markers including TCR, CD4, CD8, MHC-Ⅰ and MHC-Ⅱ were examined. Results The data showed that the immune response to either vector stock reached maximal levels by 4 to 7 days after gene transfer. However, the maximal levels of all markers to the helper virus-free stock were 3 to 10 folds lower than the markers to the helper virus stock. The immune response to the helper virus-free stock declined rapidly to be close to the levels of PBS control. Conclusion The immune response to the helper virus-free stock is significantly less than the response to the vector stock that contains helper virus.