The possible use of HLA-G1 and G3 in the inhibition of NK cell-mediated swine endothelial cell lysis
Autor: | Shuji Miyagawa, R Shirakura, A Murase, Katsuyoshi Matsunami, R Nakai |
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Rok vydání: | 2001 |
Předmět: |
Cytotoxicity
Immunologic Swine Blotting Western Transplantation Heterologous Immunology Cell CHO Cells Biology Transfection Cell Line Flow cytometry Natural killer cell HLA Antigens Cricetinae medicine Animals Humans Immunology and Allergy Endothelium RNA Messenger Cytotoxicity HLA-G Antigens Transplantation Expression vector medicine.diagnostic_test Chinese hamster ovary cell Histocompatibility Antigens Class I Cytotoxicity Tests Immunologic Flow Cytometry Killer Cells Natural Endothelial stem cell medicine.anatomical_structure Peptides Oligopeptides |
Zdroj: | Clinical and Experimental Immunology. 126:165-172 |
ISSN: | 1365-2249 0009-9104 |
Popis: | SummaryThe splicing isoform of HLA-G that is expressed in xenogeneic cells, and its effect on NK-mediated direct cytotoxicity was examined, using stable Chinese hamster ovary (CHO) cell or swine endothelial cell (SEC) transfectants. cDNAs of HLA-G (G1 and G3) and human β2-microglobulin were prepared and subcloned into the expression vector, pCXN. The transfected HLA-G1 was easily expressed on SEC, and co-transfection with human β2-microglobulin led to an enhanced level of HLA-G1 expression, as evidenced by flow cytometry. The expressed HLA-G1 significantly suppressed NK-mediated SEC cell lysis, which is an in vitro delayed-type rejection model of a xenograft. On the other hand, the swine leucocyte antigen (SLA) class I molecules could be up-regulated as the result of the transfection of human β2-microglobulin, but did not down-regulate human NK-mediated SEC lysis. The HLA-G3 was not expressed on CHO and SEC in contrast to HLA-G1, as the result of the transfection. The gene introduction of HLA-G3 in SEC showed no protective effect from human NK cells. However, indirect evidence demonstrated that HLA-G3 transfection resulted in HLA-E expression, but not itself, when transfected to the human cell line, 721.221, thus providing some insight into its natural function in human cells. The present findings suggest that the expression of HLA-G1 on the cell surface could serve as a new approach to overcoming NK-mediated immunity to xenografts. |
Databáze: | OpenAIRE |
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