Peripheral Cellular Immune Responses Induced by Subretinal Adeno-Associated Virus Gene Transfer Can Be Restrained by the Subretinal-Associated Immune Inhibition Mechanism.

After more than two decades of basic research and preclinical studies, adeno-associated virus (AAV)-mediated gene transfer has been tested successfully in clinical trials to treat inherited retinal diseases. Despite the eye's immune-privileged status, some patients display inflammatory events requiring the use of corticoids as an adjunct treatment which led us to question the immune consequences of a subretinal AAV administration. We first characterized anti-transgene immune responses induced in the periphery by injecting increasing doses of AAV8 encoding reporter proteins fused with the HY male antigen into the subretinal space of female C57BL/6 and rd10 mice.

Subretinal Injection of HY Peptides Induces Systemic Antigen-Specific Inhibition of Effector CD4 and CD8 T-Cell Responses.

Purpose: Injection of an antigen into the anterior chamber of the eye induces a peripheral antigen-specific immune modulation mechanism, known as anterior chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity experiments argue that the subretinal space (SR) of the eye displays properties similar to ACAID. However, no investigation was performed regarding the differential impact of a subretinal antigen injection on peripheral CD4 versus CD8 T cells, on the potential immune deviation regarding Th profiles, and on the antigen-specificity of the inhibition.

Cellular and Molecular Mechanisms of Anterior Chamber-Associated Immune Deviation (ACAID): What We Have Learned from Knockout Mice.

Anterior chamber-associated immune deviation (ACAID) is a well-known phenomenon that can occur after an antigen is introduced without any danger signal into the anterior chamber of a murine eye. It is reported to lead to an antigen-specific immune deviation throughout the body. Despite the relatively little evidence of this phenomenon in humans, it has been suggested as a potential prophylactic strategy in allograft rejections and in several autoimmune diseases.