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Role and expression of CD40 on human retinal pigment epithelial cells.
Invest Ophthalmol Vis Sci. 2000 Oct; 41(11):3485-91.IO

Abstract

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 [(3)H]-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 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.

CONCLUSIONS

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.

Authors+Show Affiliations

I.R.I.B.H.N., Campus Erasme, Université Libre de Bruxelles, Faculty of Medicine, Brussels, Belgium. fwillermain@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11006243

Citation

Willermain, F, et al. "Role and Expression of CD40 On Human Retinal Pigment Epithelial Cells." Investigative Ophthalmology & Visual Science, vol. 41, no. 11, 2000, pp. 3485-91.
Willermain F, Caspers-Velu L, Baudson N, et al. Role and expression of CD40 on human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2000;41(11):3485-91.
Willermain, F., Caspers-Velu, L., Baudson, N., Dubois, C., Hamdane, M., Willems, F., Velu, T., & Bruyns, C. (2000). Role and expression of CD40 on human retinal pigment epithelial cells. Investigative Ophthalmology & Visual Science, 41(11), 3485-91.
Willermain F, et al. Role and Expression of CD40 On Human Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2000;41(11):3485-91. PubMed PMID: 11006243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role and expression of CD40 on human retinal pigment epithelial cells. AU - Willermain,F, AU - Caspers-Velu,L, AU - Baudson,N, AU - Dubois,C, AU - Hamdane,M, AU - Willems,F, AU - Velu,T, AU - Bruyns,C, PY - 2000/9/28/pubmed PY - 2000/10/14/medline PY - 2000/9/28/entrez SP - 3485 EP - 91 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 41 IS - 11 N2 - 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 [(3)H]-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 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. CONCLUSIONS: 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. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/11006243/Role_and_expression_of_CD40_on_human_retinal_pigment_epithelial_cells_ L2 - https://iovs.arvojournals.org/article.aspx?volume=41&issue=11&page=3485 DB - PRIME DP - Unbound Medicine ER -