HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Willermain, F. Articles by Bruyns, C. Search for Related Content PubMed PubMed Citation Articles by Willermain, F. Articles by Bruyns, C.

Role and Expression of CD40 on Human Retinal Pigment Epithelial Cells

¹ From the I.R.I.B.H.N., Campus Erasme; the ² Department of Ophthalmology, CHU Saint–Pierre; and the ³ Laboratory of Experimental Immunology, Campus Erasme, Université Libre de Bruxelles, Faculty of Medicine, Brussels, Belgium.

PURPOSE. To examine the CD40 costimulatory molecule expression on normal resting or activated adult human retinal pigment epithelium (hRPE) cells and to evaluate its role as an activation molecule considering the potential antigen presentation functions of hRPE cells.

METHODS. Expression of HLA-DR and costimulatory (CD40, B7.1, B7.2, CD54, and CD58) molecules on hRPE cells was analyzed by flow cytometry. CD40 triggering 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 hRPE cells was assessed by coculturing hRPE cells with allogeneic T cells. T-cell proliferation was measured by [³H]-thymidine incorporation, and T-cell apoptosis by measurement of caspase-3 activity.

RESULTS. Interferon (IFN)-activated hRPE cells expressed CD40, but not B7.1 or B7.2. Although interferon enhanced IL-6 and IL-8 production, CD40 triggering of IFN-activated hRPE cells did not induce IL-12 secretion. hRPE cells did not stimulate allogeneic resting T cells and downregulated phytohemagglutinin-activated allogeneic T cells via a cell-to-cell contact–dependent mechanism. Some induction of apoptosis was detected.

CONCLUSIONS. CD40 is expressed on IFN-activated hRPE cells. Its ligation leads to an increased production of IL-6 and IL-8 but fails to induce B7.1 or B7.2 expression, or to induce IL-12 secretion. Accordingly, hRPE cells do not activate allogenic T cells but inhibit T-cell proliferation, partly through induction of apoptosis. These results suggest that hRPE cells could be implicated more in a deviant antigen presentation. If the exact molecular mechanisms are unclear, it is likely that CD40–CD40L interaction could play a role in this process.

This article has been cited by other articles:

				D. S. Gregerson, N. D. Heuss, K. L. Lew, S. W. McPherson, and D. A. Ferrington Interaction of Retinal Pigmented Epithelial Cells and CD4 T Cells Leads to T-Cell Anergy Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4654 - 4663. [Abstract] [Full Text] [PDF]

				N. M. McKechnie, D. Copland, and G. Braun Hr44 Secreted with Exosomes: Loss from Ciliary Epithelium in Response to Inflammation Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2650 - 2656. [Abstract] [Full Text] [PDF]

				M. D. Silverman, D. O. Zamora, Y. Pan, P. V. Texeira, S.-H. Baek, S. R. Planck, and J. T. Rosenbaum Constitutive and Inflammatory Mediator-Regulated Fractalkine Expression in Human Ocular Tissues and Cultured Cells Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1608 - 1615. [Abstract] [Full Text] [PDF]

				F Willermain, L Caspers-Velu, B Nowak, P Stordeur, R Mosselmans, I Salmon, T Velu, and C Bruyns Retinal pigment epithelial cells phagocytosis of T lymphocytes: possible implication in the immune privilege of the eye Br. J. Ophthalmol., December 1, 2002; 86(12): 1417 - 1421. [Abstract] [Full Text] [PDF]

				M. Iwata, K. Soya, M. Sawa, T. Sakimoto, and D. G. Hwang CD40 Expression in Normal Human Cornea and Regulation of CD40 in Cultured Human Corneal Epithelial and Stromal Cells Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 348 - 357. [Abstract] [Full Text] [PDF]

				N. Kanuga, H. L. Winton, L. Beauchene, A. Koman, A. Zerbib, S. Halford, P.-O. Couraud, D. Keegan, P. Coffey, R. D. Lund, et al. Characterization of Genetically Modified Human Retinal Pigment Epithelial Cells Developed for In Vitro and Transplantation Studies Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 546 - 555. [Abstract] [Full Text] [PDF]