Immune responses to adenoviral vectors during gene transfer in the brain.
Immune responses to adenoviral vectors during gene transfer in the brain.
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大脑基因转移期间对腺病毒载体的免疫反应。
作者：
Koji Kajiwara;A.P Byrnes;H. M. Charlton;Matthew J.A. Wood;Kathryn J. Wood
我们已经研究了对E1缺失腺病毒载体的免疫应答，所述腺病毒载体编码引入成年小鼠脑中的lacZ基因。通过免疫细胞化学和流式细胞术对白细胞进行评估，注射这些非复制型载体在脑中引起显著的炎症反应。在注射后2天内可检测到浸润的白细胞，并在9天达到最大值。此后，浸润细胞的数量减少，但少量细胞持续存在于脑中，直到第60天。在注射后2至4天之间，可检测到的CD 8+细胞的百分比增加，而浸润群体中存在的CD 4+细胞的百分比直到第6天才显著增加，在第15天达到峰值。活化的CD 25 + T细胞在第6 - 15天可检测到。在纹状体和黑质的注射部位也检测到β-半乳糖苷酶（β-Gal），即载体编码的lacZ基因的产物。表达在4至6天之间达到峰值，但在注射后60天仍观察到少量β-Gal+细胞。这项研究表明，定量分析的免疫反应引起的非复制型腺病毒载体是可能的，在大脑中。E1缺失的腺病毒载体在大脑中引发强烈的炎症反应，但这种免疫反应不足以完全消除腺病毒构建体编码的基因的表达。
We have investigated the immune response to E1-deleted adenovirus vectors encoding the lacZ gene introduced into the brains of adult mice. Injection of these nonreplicating vectors caused a marked inflammatory response in the brain as assessed by immunocytochemistry and flow cytometry of leukocytes. Infiltrating leukocytes were detectable within 2 days of injection and reached a maximum by 9 days. Thereafter, the number of infiltrating cells decreased, but a small number persisted in the brain until day 60. Between 2 and 4 days after injection, the percentage of CD8+ cells detectable increased whereas the percentage of CD4+ cells present in the infiltrating population did not significantly increase until day 6, peaking on day 15. Activated CD25+ T cells were detectable between days 6 and 15. beta-Galactosidase (beta-Gal), the product of the lacZ gene encoded by the vector, was also detected, both at the injection site in the striatum and also in the substantia nigra. Expression peaked between 4 and 6 days but a small number of beta-Gal+ cells was still seen at 60 days after injection. This study demonstrates that a quantitative analysis of the immune responses caused by a nonreplicating adenovirus vector is possible in the brain. E1-deleted adenoviral vectors trigger a strong inflammatory response in the brain, but this immune response is not sufficient to eliminate completely expression of genes encoded by the adenoviral construct.
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将重组腺病毒立体定向递送至大鼠脑肿瘤模型中的 C6 神经胶质瘤细胞系。
影响因子：
4.8
作者：
Badie,B;Hunt,K;Economou,JS;Black,KL
通讯作者：
Black,KL
发育阶段、给药途径和免疫系统对腺病毒介导的基因转移的影响。
影响因子：
5.1
作者：
Kass-Eisler,A;Falck-Pedersen,E;Elfenbein,DH;Alvira,M;Buttrick,PM;Leinwand,LA
通讯作者：
Leinwand,LA
DOI：
10.1073/pnas.91.10.4407
发表时间：
1994-05-10
影响因子：
11.1
作者：
YANG, YP;NUNES, FA;WILSON, JM
通讯作者：
WILSON, JM
病毒性脑炎的免疫反应。
影响因子：
7.8
作者：
Griffin,DE;Levine,B;Tyor,WR;Irani,DN
通讯作者：
Irani,DN
DOI：
10.1073/pnas.88.5.1651
发表时间：
1991-03-01
影响因子：
11.1
作者：
GINSBERG, HS;MOLDAWER, LL;PRINCE, GA
通讯作者：
PRINCE, GA