T-cell response to adenovirus hexon and DNA-binding protein in mice
T-cell response to adenovirus hexon and DNA-binding protein in mice
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DOI：
10.1038/sj.gt.3302232
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发表时间：
2004-05-01
期刊：
影响因子：
5.1
通讯作者：
Chastain, M
中科院分区：
文献类型：
--
作者：
McKelvey, T;Tang, A;Chastain, M
成功开发用于疫苗和基因治疗的腺病毒载体将需要更好地了解宿主免疫应答。利用ELISPOT检测IFN-γ分泌的CD 8（+）细胞，我们在BALB/c和C57 BL/6小鼠中鉴定了腺病毒六邻体和DNA结合蛋白的免疫显性表位。对肌内施用腺病毒血清型5的T细胞应答在几周内达到峰值，并逐渐下降，但在12周后仍可检测到。第二次给药没有显著增加反应性T细胞的数量。野生型和E1缺失腺病毒的CD 8（+）T细胞应答也相似。当B细胞缺陷小鼠注射腺病毒编码的基因分泌碱性磷酸酶，血清磷酸酶活性降低更快地在小鼠预先暴露于腺病毒。这些结果增加了细胞介导的免疫是治疗性腺病毒载体的实质性障碍的证据，并提供了更多的定量工具来测量对腺病毒的细胞免疫应答。
The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 mice. The T-cell response to the intramuscular administration of adenovirus serotype 5 peaks within a few weeks and gradually declines but is still detectable after 12 weeks. A second administration did not substantially increase the number of reactive T cells. The CD8(+) T-cell response was also similar between wild type and E1-deleted adenovirus. When B-cell-deficient mice were injected with adenovirus encoding the gene for secreted alkaline phosphatase, sera phosphatase activity was reduced more quickly in mice pre-exposed to adenovirus. These results add to the evidence that cell-mediated immunity is a substantial barrier to therapeutic adenoviral vectors and provide more quantitative tools to measure cellular immune responses to adenovirus.