Autoimmunity in the immune privileged eye: pathogenic and regulatory T cells

Experimental autoimmune uveitis (EAU) in animals serves as a model of human uveitis. EAU can be induced in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) in complete Freund's adjuvant (CFA) or by IRBP-pulsed mature dendritic cells, and can be driven either by a Th17 or a Th1 effector response, depending on the model. The direction of the response is affected by conditions present during the exposure to antigen, including the quality/quantity of innate receptor stimulation and/or type of APC. IL-17 and IFN-gamma production by innate cells such as NKT may also affect the disease process. If exposure to antigen is via a hydrodynamic DNA vaccination with an IRBP-encoding plasmid, the response is directed to a regulatory phenotype, and disease is ameliorated or prevented. Our data shed light on effector and regulatory responses in autoimmune disease, provide balance to the Th1/Th17 paradigm and help to explain the clinical heterogeneity of human uveitis, which occurs in the face of responses to the same ocular antigen(s).