Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells attenuates human NK cell-mediated degranulation

نویسندگان

چکیده

Natural killer (NK) cells play an important role in immune rejection solid organ transplantation. To mitigate human NK cell activation xenotransplantation, introducing inhibitory ligands on xenografts via genetic engineering of pigs may protect the graft from cell-mediated cytotoxicity and ultimately improve xenograft survival. In this study, non-classical HLA class I molecules HLA-E HLA-G were introduced immortalized porcine liver endothelial line with disruption five genes ( GGTA1 , CMAH β4galNT2 SLA-I α chain β-2 microglobulin ) encoding three major carbohydrate xenoantigens (αGal, Neu5Gc, Sda) swine leukocyte antigen (SLA-I) molecules. Expression and/or pig confirmed by flow cytometry. Endogenous as well exogenous VL9 peptide could dramatically enhance expression transfected cells. We found that co-expression led to a significant reduction compared expressing or alone parental line. was assessed analysis CD107a CD3 - CD56 + population gated peripheral blood mononuclear is sensitive marker correlates degranulation cytotoxicity. did not show reactivity sera IgG IgM antibodies. This vitro study demonstrated genetically modified provided superior inhibition xenoreactive cells, which guide further prevent mediated rejection.

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ژورنال

عنوان ژورنال: Frontiers in Immunology

سال: 2023

ISSN: ['1664-3224']

DOI: https://doi.org/10.3389/fimmu.2023.1217809