A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus

被引：58

作者：

Anand, V ^{[1
]}

Duffy, B ^{[1
]}

Yang, ZX ^{[1
]}

Dejneka, NS ^{[1
]}

Maguire, AM ^{[1
]}

Bennett, J ^{[1
]}

机构：

[1] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, Stellar Chance Labs 310, Philadelphia, PA 19104 USA

来源：

MOLECULAR THERAPY | 2002年 / 5卷 / 02期

关键词：

adenovirus; adeno-associated virus; subretinal space; immune privilege; immune deviation;

D O I：

10.1006/mthe.2002.0525

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The immune response after ocular exposure to foreign antigens varies substantially from that of a typical systemic response. Anterior chamber associated immune deviation (ACAID) has been well documented. The immune response of the subretinal space has not been studied in as much detail. Here, we characterized the immune response of the subretinal space when it encounters the antigens AdV-GFP and AAV-GFP (recombinant adenovirus or adeno-associated virus, respectively), each delivering the reporter gene encoding green fluorescent protein (GFP). Results indicate that the subretinal space possesses an immune-deviant property similar to ACAID. AdV-elicited immune responses following subretinal injections are significantly reduced compared with systemic responses elicited by intradermal injections of the same virus. Furthermore, subretinal AdV administration results in transduction of retinal pigment epithelial cells (RPE), which are the potential antigen presenting cells of the retina. This subsequently generates a population of immunosuppressive Th2-type, cytokine-secreting, splenic T cells. This response may be advantageous to the development of ocular gene therapy.

引用

页码：125 / 132

页数：8

共 30 条

[1] Co-injection of adenovirus expressing CTLA4-Ig prolongs adenovirally mediated lacZ reporter gene expression in the mouse retina [J].