title: CD8(+) T-cell responses to adeno-associated virus capsid in humans.
abstract: 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.
authors: The Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, Pennsylvania 19104, USA.
authors: Federico
authors: F
authors: Mingozzi
authors: Marcela V
authors: MV
authors: Maus
authors: Daniel J
authors: DJ
authors: Hui
authors: Denise E
authors: DE
authors: Sabatino
authors: Samuel L
authors: SL
authors: Murphy
authors: John E J
authors: JE
authors: Rasko
authors: Margaret V
authors: MV
authors: Ragni
authors: Catherine S
authors: CS
authors: Manno
authors: Jurg
authors: J
authors: Sommer
authors: Haiyan
authors: H
authors: Jiang
authors: Glenn F
authors: GF
authors: Pierce
authors: Hildegund C J
authors: HC
authors: Ertl
authors: Katherine A
authors: KA
authors: High
mesh_terms: 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
chemical_list: D010455:Peptides