Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming
Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming
复制标题
大脑中腺病毒载体免疫反应的变化：小鼠品系、环境条件和启动的影响
作者：
Y. Ohmoto;M. Wood;H. Charlton;K. Kajiwara;V. Perry;K. Wood
将表达细菌β-半乳糖苷酶基因的E1缺失的腺病毒载体接种到在常规或无特异性病原体（SPF）条件下饲养的未致敏和致敏的C3H.He或C57 BL/6 J小鼠的脑中。研究了对载体和转基因两者的免疫应答的动力学。在先前对腺病毒致敏的小鼠中，脑中的白细胞浸润以CD 8 + T细胞为主，而在未致敏的小鼠中，CD 4 + T细胞以较高水平存在。正如预期，颅内接种后，致敏小鼠中对腺病毒和β-半乳糖苷酶的抗体滴度均高于未致敏小鼠。C3H.He小鼠的抗体应答明显高于C57 BL/6 J小鼠。尽管腺病毒载体在所有条件下都能诱导炎症反应，但SPF设施中的小鼠比常规小鼠表现出更少的炎症，并且转基因表达持续时间更长。无论小鼠是否被故意引发腺病毒，SPF小鼠的抗体滴度始终低于常规小鼠。这项研究清楚地表明，环境条件，以及以前的启动腺病毒，将影响基因传递到大脑引发的免疫反应的质量和持续时间。
E1-deleted adenoviral vectors expressing the bacterial β-galactosidase gene were inoculated into the brain of unprimed and primed C3H.He or C57BL/6J mice housed under either conventional or specific-pathogen-free (SPF) conditions. The kinetics of immune responses to both the vector and the transgene were investigated. In mice previously sensitized to adenovirus, the leukocyte infiltrate in the brain was dominated by CD8+ T cells, whereas in unprimed mice CD4+ T cells were present at higher levels. As expected, antibody titres to both adenovirus and β-galactosidase were higher in primed mice than in unprimed mice after intracranial inoculation. C3H.He mice consist- ently made higher antibody responses than C57BL/6J mice. Although adenoviral vectors induced an inflammatory response under all conditions, mice housed in SPF facilities exhibited less inflammation than conventional mice and transgene expression persisted for longer. Irrespective of whether the mice had been deliberately primed to adenovirus, antibody titres were consistently lower in SPF mice compared with conventional mice. This study clearly demonstrates that environmental conditions, as well as previous priming to adenovirus, will affect both the quality and duration of the immune response triggered by gene delivery to the brain.
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DOI：
--
发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Yang,H;Welsh,RM
通讯作者：
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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：
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影响因子：
4.4
作者：
F. Rawle;B. Knowles;R. Ricciardi;V. Brahmacheri;P. Duerksen-Hughes;W. Wold;L. Gooding
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F. Rawle;B. Knowles;R. Ricciardi;V. Brahmacheri;P. Duerksen-Hughes;W. Wold;L. Gooding
抗病毒CTL前体的体内状态。
DOI：
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发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Razvi,ES;Welsh,RM;McFarland,HI
通讯作者：
McFarland,HI
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DOI：
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发表时间：
1995
期刊：
Gene therapy.
影响因子：
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作者：
Barr,D;Tubb,J;Ferguson,D;Scaria,A;Lieber,A;Wilson,C;Perkins,J;Kay,MA
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Kay,MA