HLA-G expression protects porcine endothelial cells against natural, killer cell-mediated xenogeneic cytotoxicity

Hitomi Sasaki, Xiao Chun Xu, Douglas M. Smith, Todd Howard, T. Mohanakumar

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background. Natural killer (NK) cells are major component of the cellular response in xenotransplantation. NK cell activation and NK cell- mediated cytotoxicity can be a direct barrier to the potential use of xenogeneic organs in human transplantation. Methods. To determine if HLA-G would protect porcine xenogeneic cells from human NK cell lysis, human full- length HLA-G genomic DNA was transfected into porcine aortic endothelial cell (PAECs) by the lipofection method. Surface expression of HLA-G in transfected PAECs was confirmed by immunofluorescense staining with anti-HLA class I framework antibody, PA2.6. Fresh human peripheral blood lymphocytes were used as NK effector cells with HLA-G-transfected PAECs as targets in a 51Cr release assay. The inhibition of human polyclonal NK cells by HLA-G expression on PAECs was confirmed by antibody blocking using purified F(ab')2 portion of anti-human HLA class I antibody PA2.6. Results. Expression of HLA- G on PAECs conferred a significant protection against NK-mediated lysis (range: 52-100% inhibition) when peripheral blood lymphocytes from seven healthy donors, bearing either homozygous HLA-Cw3 or -Cw4 used as NK effector cells. Such protection was inhibited by purified F(ab')2 portion of anti-HLA class I antibody, indicating that the protection of PAECs was directly mediated by HLA-G expression. Conclusions. Expression of HLA-G on PAECs protected xenogeneic PAECs against human polyclonal NK cell-mediated lysis. These results indicate that the expression of HLA-G alone in the absence of other nonclassical HLA class I molecules is sufficient to inhibit human NK cell lysis. These findings suggest methods utilizing HLA-G to overcome NK cell-mediated cytotoxicity against porcine endothelial cells, considered the first cell type effected during xenograft cellular rejection.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalTransplantation
Volume67
Issue number1
DOIs
Publication statusPublished - 15-01-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Transplantation

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