CD8(+) T-cell responses to adeno-associated virus capsid in humans.
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.
Mingozzi
Federico
F
The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
Maus
Marcela V
MV
Hui
Daniel J
DJ
Sabatino
Denise E
DE
Murphy
Samuel L
SL
Rasko
John E J
JE
Ragni
Margaret V
MV
Manno
Catherine S
CS
Sommer
Jurg
J
Jiang
Haiyan
H
Pierce
Glenn F
GF
Ertl
Hildegund C J
HC
High
Katherine A
KA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D000229:Dependovirus / Q000276:immunology*; D018014:Gene Transfer Techniques; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010322:Parvoviridae Infections / Q000276:immunology*; D010455:Peptides / Q000276:immunology
D010455:Peptides