Participation of pigment epithelium in ocular immune privilege. 3. Epithelia cultured from iris, ciliary body, and retina suppress T-cell activation by partially non-overlapping mechanisms

Abstract

Purpose: The ocular microenvironment is immunosuppressive and anti-inflammatory. Since various ocular pigmented epithelia contribute to this microenvironment, we studied the relative capacities of pigment epithelial (PE) cells cultured from the iris, ciliary body, and retina of mouse eyes to suppress T-cell activation in vitro.

Methods: Pigment epithelium was cultured from iris, ciliary body, and retina for 14 days, then assayed for the capacity, directly or across transwell membranes, to suppress mixed lymphocyte reactions and anti-CD3 stimulation of T cells. Potential molecules responsible for suppression were examined by attempting to block suppression with appropriate reagents, and by using mice with pertinent mutant or disrupted genes.

Results: We found that PE cells from all three ocular tissue sources profoundly suppressed T-cell activation in vitro. While iris PE suppressed poorly when separated from T cells by a transwell membrane (implying that cell contact is necessary), retina PE suppressed fully even in the presence of such a membrane (implying that soluble factors were responsible). Ciliary body PE used both soluble factors as well as cell contact to achieve suppression. Suppression could not be ascribed to TGFbeta, IFNgamma, TNFalpha, CD48, or ICAM-1, or to interactions between CD40 and CD154, or CD95 and CD95 ligand. Galectin-1, a galactoside-binding protein, was found to be expressed on all cultured PE cells, but only retinal pigment epithelium (RPE) from galectin-1 KO mice showed reduced capacity to inhibit T-cell activation.

Conclusions: Cultured pigment epithelia from iris, ciliary body, and retina comparably suppress T-cell activation in vitro, but by partially different mechanisms. Although RPE cells suppress in part through expression of galectin-1, the molecular mediators of suppression by iris and ciliary body PE remain to be identified.