Role and expression of CD40 on human retinal pigment epithelial cells

PURPOSE. To examine the CD40 costimulatory molecule expression on normal re sting or activated adult human retinal pigment epithelium (hRPE) cells and to evaluate its role as an activation molecule considering the potential an tigen presentation functions of hRPE cells. METHODS. Expression of HLA-DR and costimulatory (CD40, B7.1, B7.2, CD54, an d CD58) molecules on hRPE cells was analyzed by flow cytometry. CD40 trigge ring was performed using soluble CD40L or cocultures with CD40L transfected fibroblasts. Interleukin (IL)-6, -8, -10, and -12 secretions were measured by enzyme-linked immunosorbent assay. Antigen presentation function of hRP E cells was assessed by coculturing hRPE cells with allogeneic T cells. T-c ell proliferation was measured by [H-3]-thymidine incorporation, and T-cell apoptosis by measurement of caspase-3 activity. RESULTS. Interferon (IFN)gamma-activated hRPE cells expressed CD40, but not B7.1 or B7.2. Although interferon gamma enhanced IL-6 and IL-8 production, CD40 triggering of IFN gamma-activated hRPE cells did not induce IL-12 sec retion. hRPE cells did not stimulate allogeneic resting T cells and downreg ulated phytohemagglutinin-activated allogeneic T cells via a cell-to-cell c ontact-dependent mechanism. Some induction of apoptosis was detected. CONCLUSIONS. CD40 is expressed on IFN gamma-activated hRPE cells. Its ligat ion leads to an increased production of IL-6 and IL-8 but fails to induce B 7.1 or B7.2 expression, or to induce IL-12 secretion. Accordingly, hRPE cel ls do not activate allogenic T cells but inhibit T-cell proliferation, part ly through induction of apoptosis. These results suggest that hRPE cells co uld be implicated more in a deviant antigen presentation. If the exact mole cular mechanisms are unclear, it is likely that CD40-CD40L interaction coul d play a role in this process.