Role and expression of CD40 on human retinal pigment epithelial cells
| Autor: | Willermain F, Caspers-Velu L, Baudson N, Dubois C, Malika Hamdane, Willems F, Velu T, Bruyns C |
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| Rok vydání: | 2000 |
| Předmět: |
Antigen Presentation
Membrane Glycoproteins Caspase 3 T-Lymphocytes CD40 Ligand Antigen-Presenting Cells Apoptosis HLA-DR Antigens Fibroblasts Flow Cytometry Lymphocyte Activation Coculture Techniques Up-Regulation Interferon-gamma Mice Antigens CD Caspases Animals Cytokines Humans CD40 Antigens Pigment Epithelium of Eye Cell Adhesion Molecules Cells Cultured |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0146-0404 |
| Popis: | 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.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 [(3)H]-thymidine incorporation, and T-cell apoptosis by measurement of caspase-3 activity.Interferon (IFN)gamma-activated hRPE cells expressed CD40, but not B7.1 or B7.2. Although interferongamma enhanced IL-6 and IL-8 production, CD40 triggering of IFNgamma-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.CD40 is expressed on IFNgamma-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. |
| Databáze: | OpenAIRE |
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