Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4spi+CD25hiFoxp3+ Treg cells

Qing Ding, Liming Lu, Xiaorong Zhou, Yun Zhou, Kuang Yen Chou

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

In xenotransplantation models, direct activation of hCD4+ T cells by porcine VECs leads to a robust proliferation of T cells. To investigate the underlying mechanisms, human antiporcine MLEC culture was used to investigate crossspecies cell interactions, proliferation of hCD4+ T cells, and induction of human cytokines. We report that xenoantigen presentation by PIEC expands hCD4+ Foxp3+ Tregs and hCD4+ Foxp3-Teffs, and this process is dependent on porcine MHC-II antigen expression. Stable transfection of hPD-L1 into PIEC inhibits Teff proliferation, but Treg proliferation is not affected. Surprisingly, IL-10 production by hCD4+ T cells is augmented significantly by PIEChPD-L1. Notably, hPD-L1-induced Tregs have higher suppressive potency and mediate suppressive function partially through IL-10 and CD73. This study opens the possibility of using hPD-L1-overexpressing porcine VECs as a novel therapeutic to allow tolerance of xenotransplants and also supports the possibility of using hPD-L1 transgenic pigs as xenotransplant donors.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalJournal of Leukocyte Biology
Volume90
Issue number1
DOIs
StatePublished - Jul 1 2011

    Fingerprint

Keywords

  • CD73 (ecto-5′-nucleotidase)
  • IL-10
  • Negative costimulation
  • PD-1
  • Regulatory T cells
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Cite this