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P. Zamiri, J.W. Streilein; RPE Cells Secrete Soluble Factors Ex Vivo That Inhibit Neutrophil Activation and Prevent NK Cell-Mediated Cytotoxicity . Invest. Ophthalmol. Vis. Sci. 2003;44(13):739.
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Purpose: Retinal pigment epithelial cells (RPE) are known to secrete factors that suppress T cell activation (adaptive immunity). The purpose of these experiments was to determine whether soluble factors produced by explanted retinal pigment epithelium (RPE) could also inhibit innate immune cell functions. Methods: An ex-vivo model of the posterior eyecup was produced, in which the anterior segment, lens, and retina were excised from enucleated eyes of adult C57BL/6 mice, leaving for study the sclera, choroid and a healthy monolayer of RPE. Serum free medium was added to these RPE eyecups and supernatants (SN) were removed after 24 hours and added to the following assays: (a) casein-stimulated neutrophils were cultured in vitro and their supernatants assayed for IL-1ß release, using an ELISA; (b) NK cells, obtained from spleens of BALB/c mice treated with poly I:C, were assayed for their capacity to lyse YAC-1 tumor cells. Neutralizing anti-TGF-ß antibodies were added to some cultures to determine the role of this cytokine in the observed inhibition. Results: Supernatants from RPE eyecups inhibited IL-1ß production by activated neutrophils, and this inhibition was partially relieved in the presence of anti-TGF-ß antibodies. RPE SN also significantly inhibited the capacity of NK cells to lyse YAC-1 target cells. Conclusions: RPE cells secrete soluble factors that inhibit activation of innate immune cells – neutrophils and NK cells. TGF-ß, a constituent of RPE supernatants, accounts at least in part for the inhibition of innate and adaptive immune cell activation. Thus, the RPE-dependent immune privilege of the subretinal space may involve inhibition of innate, as well as adaptive, immunity.
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