Aqueous Humor Suppression of Dendritic Cell Function Helps Maintain Immune Regulation in the Eye during Human Uveitis

PURPOSE. Noninfectious uveitis is characterized by a dysregulated inflammatory or immune response in the eye. It is unclear whether this represents a failure of immune privilege or an overwhelming inflammatory drive that has exceeded the capacity of regulatory mechanisms that are still functioning. The authors investigated immune regulation in the human eye during intraocular inflammation (uveitis) and its impact on dendritic cell (DC) function and subsequent T-cell responses. METHODS. Myeloid DCs were isolated from the aqueous humor (AqH) and peripheral blood of patients with active uveitis and characterized by flow cytometry. The effect of uveitis AqH was interrogated in an in vitro model of peripheral blood monocyte-derived DCs from healthy controls. RESULTS. Myeloid DCs isolated from uveitic AqH were characterized by elevated major histocompatibility complex classes I and II (MHC I/II), but reduced CD86 compared with matched peripheral blood DCs. Exposure of peripheral blood monocyte-derived DCs from healthy controls to the inflammatory AqH supernatant recapitulated this phenotype. Despite interferon gamma (IFN gamma)-dependent upregulation of MHC I, inflammatory AqH was overall suppressive to DC function, with reduced CD86 expression and diminished T-cell responses. This suppressive effect was equal to or greater than that induced by noninflammatory AqH, but was glucocorticoid independent (in contrast to noninflammatory AqH). CONCLUSIONS. These data indicate that the ocular microenvironment continues to regulate DC function during uveitis, despite IFN gamma-driven upregulation of MHC expression, supporting the hypothesis that immune regulation within the eye is maintained during inflammation. (Invest Ophthalmol Vis Sci. 2012; 53: 888-896) DOI: 10.1167/iovs.11-8802