期刊
NATURE MEDICINE
卷 13, 期 4, 页码 419-422出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm1549
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资金
- NCRR NIH HHS [M01-RR000056, M01-RR00240] Funding Source: Medline
- NHLBI NIH HHS [F32 HL69647, P01 HL078810, T32 HL07439] Funding Source: Medline
- NIAID NIH HHS [P30 AI045008] Funding Source: Medline
- NIDDK NIH HHS [T32 DK07748] Funding Source: Medline
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.
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