Retinal pigment epithelial (RPE) cells form an important part of the blood-retinal barrier that protects the neuronal cells responsible for sight. RPE cells are involved in innate and adaptive immune responses via expression of surface molecules and release of cytokines. However, RPE cells under normal conditions are anti-inflammatory, a function linked to expression of molecules such as FasL and the release of immunosuppressive molecules. In this paper the authors show that CD73, a GPI-anchored nucleotidase expressed on RPE cells abrogated immune responses in the animal model experimental autoimmune uveoretinitis. Proinflammatory adenosine triphosphate (ATP) is released during inflammation and is converted to adenosine monophosphate (AMP) by CD39 and to anti-inflammatory adenosine by CD73. The results show that normal mouse RPE shows strong expression of CD73, which was significantly reduced in inflamed eyes or RPE from inflamed eyes. In an in vitro chamber assay CD73-poitive RPE cells inhibited T cell activation on addition of AMP, whereas CD73-negative cells did not. CD73 has been described as a marker of regulatory T cells and this paper demonstrates that it performs a similar function in RPE cells to protect the retina from deleterious immune responses.