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).
Caspi
Rachel
R
NIH/UPenn Graduate Program, Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10N222, Bethesda, MD, 20892, USA. rcaspi@helix.nih.gov
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D007371:Interferon-gamma; D020381:Interleukin-17; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial