HLA-Cw4 expression on porcine endothelial cells reduces cytotoxicity and adhesion mediated by CD158a+ human NK cells
| Autor: | Jorg Dieter Seebach, Mårten K J Schneider, Bettina C. Baumann, Pietro Forte |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cytotoxicity
Immunologic Cell Adhesion/immunology Swine Immunology Cell Transplantation Heterologous HLA-C Antigens Major histocompatibility complex Flow cytometry Cell Line Killer Cells Natural/cytology/*immunology KIR2DL1 HLA-C Antigens/*metabolism medicine Cell Adhesion Endothelium Vascular/cytology/*immunology Animals Humans Cytotoxicity Immunologic/*immunology Cell adhesion Cytotoxicity Swine/*immunology ddc:616 Transplantation Receptors KIR2DL1/*metabolism biology medicine.diagnostic_test Receptors KIR2DL3/metabolism Transfection Cell biology Killer Cells Natural medicine.anatomical_structure Cell culture Receptors KIR2DL3 Receptors KIR2DL1 biology.protein Endothelium Vascular |
| Zdroj: | Xenotransplantation, Vol. 16, No 1 (2009) pp. 19-26 |
| ISSN: | 1399-3089 0908-665X |
| Popis: | BACKGROUND: Human natural killer (NK) cell-mediated cytotoxicity represents a hurdle in pig-to-human xenotransplantation. It was previously reported that the expression of human major histocompatibility complex class I molecules, including HLA-B27, -Cw3, -E, and -G, partially protects porcine endothelial cells (pEC) from human NK-mediated cytotoxicity and that HLA-G inhibits NK adhesion to pEC. Here, we tested if HLA-Cw4 expression on pEC alone, or concurrently with HLA-Cw3, prevents human NK adhesion and cytotoxicity against pEC via recognition of the killer-cell immunoglobulin-like receptors (KIR) CD158a (KIR2DL1) and CD158b (KIR2DL2/3), respectively. METHODS: Two pEC lines (2A2 and PEDSV.15) were transfected with HLA-Cw3 and HLA-Cw4. HLA and KIR expression on porcine and human cells were analyzed by flow cytometry. The effect of HLA expression on pEC on human NK-mediated cytotoxicity and adhesion was tested by (51)Cr-release and dynamic adhesion assays, respectively. Results: HLA-Cw4 expression on pEC reduced cytotoxicity mediated by CD158a(+) polyclonal human NK cells by an average of 58%, and by CD158a(bright) NK cell clones by 68%, but not by NK cells expressing low levels of CD158. Co-expression of HLA-Cw3 and HLA-Cw4 on pEC did not mediate further protection against NK cytotoxicity. The expression of HLA-Cw4 reduced the adhesion of human NK cells on pEC by a mean of 53%. CONCLUSIONS: While transgenic expression of HLA-Cw4 on pEC reduces NK cell adhesion and cytotoxicity, co-expression with HLA-Cw3 is not sufficient to completely overcome human NK-mediated cytotoxicity in vitro. |
| Databáze: | OpenAIRE |
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