A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus.
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.
Anand
Vibha
V
Univeristy of Pennsylvania, F. M. Kirby Center for Molecular Ophthalmology, 310 Stellar Chance Labs, Scheie Eye Institute, 422 Curie Blvd, Philadelphia, Pennsylvania 19104-6069, USA.
Duffy
Bethany
B
Yang
Zaixin
Z
Dejneka
Nadine S
NS
Maguire
Albert M
AM
Bennett
Jean
J
D000256:Adenoviridae / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D000229:Dependovirus / Q000737:chemistry / Q000276:immunology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012160:Retina / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D008164:Luminescent Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; D049452:Green Fluorescent Proteins