Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes.

Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Research Abstract Details 

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Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Abstract Text:

The goal of these studies was to test whether adeno-associated virus (AAV) capsid-specific CD8(+) T cells cause loss of hepatic AAV-mediated gene expression in experimental animals. Mice immunized with adenoviral vectors expressing AAV capsid or with AAV vectors developed CD8(+) T cells in blood, lymphatic tissues, and liver to epitopes shared between AAV2 and AAV8, and serotype-specific neutralizing antibodies. At the height of the T cells' effector phase, mice were infused with a heterologous AAV vector expressing human factor IX under a hepatocyte-specific promoter. Despite the presence of lytic CD8(+) T cells in the liver, hepatic Factor IX expression was sustained and comparable in AAV-preimmune and naïve animals. These results suggest that, in mice, pre-existing CD8(+) T cells to AAV capsid do not affect the longevity of AAV-mediated hepatic gene transfer. These results are in contrast to the outcome of a recent gene therapy trial of hemophilia B patients who were treated by hepatic gene transfer of AAV2 vectors expressing Factor IX. The loss of Factor IX expression, accompanied by a rise in liver enzymes and detectable frequencies of circulating AAV capsid-specific T cells, suggested T-cell-mediated destruction of transduced hepatocytes following reactivation of AAV-specific T cells upon AAV transfer.

Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Publishing Authors By Initials

For similar investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research

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Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 792-800

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 23

MONTH: 01

YEAR: 2007

Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100890581

Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Keywords Mesh Terms:

KEYWORDS: Transduction, Genetic

MESH TERMS: virology

Chemical & Substance for Abstract: Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Information

Substance Name: Factor IX

Registry Number: 9001-28-9

Grant and Affiliation Information for Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes.

AFFILIATION: Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: T32-DK-007748

ACRONYM: DK

MEDLINETA: Mol Ther

REFSOURCE: Mol Ther. 2007 Apr;15(4):649-50

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