CD8+ T-cell responses to adeno-associated virus capsid in humans
CD8+ T-cell responses to adeno-associated virus capsid in humans
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DOI：
10.1038/nm1549
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发表时间：
2007-04-01
期刊：
影响因子：
82.9
通讯作者：
High, Katherine A.
中科院分区：
文献类型：
--
作者：
Mingozzi, Federico;Maus, Marcela V.;High, Katherine A.
肝腺相关病毒(AAV)-血清2型介导的基因转移导致转基因产物在实验动物中持续表达，但在人类受试者中不持续表达。我们推测这是由于AAV载体重新激活的AAV衣壳特异性记忆CD8(+)T细胞对转导的肝细胞的排斥反应所致。在这里，我们展示了健康受试者携带AAV衣壳特异性CD8(+)T细胞，以及AAV介导的基因转移导致它们的扩增。在AAV介导的基因转移后，小鼠不会出现这种扩张。此外，我们发现AAV-2诱导的人类T细胞在暴露于交替的AAV血清型后增殖，表明其他血清型不太可能逃脱衣壳特异性免疫反应。
Hepatic adeno-associated virus (AAV)-serotype 2 mediated gene transfer results in transgene product expression that is sustained in experimental animals but not in human subjects. We hypothesize that this is caused by rejection of transduced hepatocytes by AAV capsid-specific memory CD8(+) T cells reactivated by AAV vectors. Here we show that healthy subjects carry AAV capsid-specific CD8(+) T cells and that AAV-mediated gene transfer results in their expansion. No such expansion occurs in mice after AAV-mediated gene transfer. In addition, we show that AAV-2 induced human T cells proliferate upon exposure to alternate AAV serotypes, indicating that other serotypes are unlikely to evade capsid-specific immune responses.