Human T cells upregulate CD69 after coculture with xenogeneic genetically-modified pig mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSC) obtained from α1,3-galactosyltransferase gene knock-out pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46 pMSC) suppress in vitro human anti-pig cellular responses as efficiently as allogeneic human MSC. We investigated the immunoregulatory effects of GTKO/CD46 pMSC on human CD4(+) and CD8(+) T cell proliferation in response to pig aortic endothelial cells (pAEC). pMSC efficiently suppressed T cell proliferation, which was associated with downregulation of granzyme B expression. No induction of CD4(+)CD25(+)Foxp3(hi) regulatory T cells or T cell apoptosis was documented. In correlation with T cell proliferation, CD25 expression was upregulated on T cells in response to pAEC but not to pMSC. In contrast, CD69 expression was upregulated on T cells in response to both pMSC and pAEC, which was associated with a significant increase in the phosphorylation of STAT5. GTKO/CD46 pMSC possibly regulate human T cell responses through modulation of CD69 expression and STAT5 signaling.

Keywords: CD69; GTKO/CD46; GTKO/hCD46; Gal; LAG-3; Mesenchymal stem cells; PBMC; Pig; STAT5; T cells; Xenotransplantation; galactose-α1,3-galactose; lymphocyte activation gene-3; pAEC; pMSC; pSTAT5; peripheral blood mononuclear cells; phosphorylated signal transducer and activator of transcription 5; pig aortic endothelial cells; pig mesenchymal stromal cells; α1,3-galactosyltransferase gene-knockout/human CD46.