PURPOSE: It is speculated that retinal pigment epithelial (RPE) cells convert naïve T cells into regulatory T cells (Tregs) via soluble factors such as transforming growth factor beta (TGF-β). Yet presence or absence of similar membrane-bound mechanisms on RPE cells has yet to be addressed. Here the authors investigated the expression of surface TGF-β by RPE cells and its participation in the conversion of naive T cells into Tregs. METHODS: They examined the phenotype of murine CD4(+) CD25(-) T cells activated in the presence of ethanol-fixed RPE cell layers as fixation preserves membrane structure while preventing the secretion of soluble factors. RESULTS: Fixed RPE cells supported the development of a de novo foxp3(+) Th3-like suppressor phenotype in activated peripheral naïve T cells through an interaction that required both RPE-derived surface TGF-β, and T-cell derived TGF-β1. CONCLUSIONS: Aside from soluble factors, RPE-derived surface TGF-β can convert activated naïve T cells into Tregs.