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François Willermain, Laure Caspers–Velu, Nathalie Baudson, Christine Dubois, Malika Hamdane, Fabienne Willems, Thierry Velu, Catherine Bruyns; Role and Expression of CD40 on Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3485-3491.
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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)γ−activated hRPE cells expressed CD40, but not B7.1
or B7.2. Although interferonγ enhanced IL-6 and IL-8 production, CD40
triggering of IFNγ−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
conclusions. CD40 is expressed on IFNγ-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
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