Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep;25(5):e12387.
doi: 10.1111/xen.12387. Epub 2018 Feb 15.

Pigs expressing the human inhibitory ligand PD-L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties

Anna Buermann  1 , Stoyan Petkov  2 , Björn Petersen  2 , Rabea Hein  1 , Andrea Lucas-Hahn  2 , Wiebke Baars  1 , Antje Brinkmann  1 , Heiner Niemann  2 , Reinhard Schwinzer  1
Affiliations

Pigs expressing the human inhibitory ligand PD-L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties

Anna Buermann et al. Xenotransplantation. 2018 Sep.

Abstract

Background: The programmed cell death-1 (PD-1, CD279)/PD-Ligand1 (PD-L1, CD274) receptor system is crucial for controlling the balance between immune activation and induction of tolerance via generation of inhibitory signals. Expression of PD-L1 is associated with reduced immunogenicity and renders cells and tissues to an immune-privileged/tolerogenic state.

Methods: To apply this concept for clinical xenotransplantation, we generated human (h)PD-L1 transgenic pigs and characterized expression and biological function of the transgene at the cellular level.

Results: The hPD-L1 was detected in kidney, heart, and pancreas. In addition, peripheral blood mononuclear cells (PBMC), cultured fibroblasts, and endothelial cells were hPD-L1 positive (hPD-L1+ ). The hPD-L1 levels were increased by the treatment of transgenic cells with human cytokines (eg, TNF-α), suggesting a regulatable mode of transgene expression. Compared to cells from wild-type pigs, hPD-L1+ PBMC had a significantly reduced capacity to stimulate proliferation of human CD4+ T cells. Moreover, fibroblasts from hPD-L1 transgenic pigs were partially protected from cell-mediated lysis by human cytotoxic effector cells.

Conclusions: These data indicate a low immunogenic, immune-protected status of cells from hPD-L1 transgenic pigs. The integration of the hPD-L1 concept into existing multi-transgenic pigs is promising to achieve long-term survival of porcine xenografts in non-human primate recipients.

Keywords: inhibitory ligands; transgenic pigs.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources