Human placenta derived mesenchymal stromal cells alleviate GVHD by promoting the generation of GSH and GST in PD-1+T cells

Abstract

Aims: To investigate whether placenta-derived mesenchymal stromal cells (hPMSCs) have immunoregulatory effects on PD-1⁺ T cell generation by controlling ROS production and thus alleviating GVHD.

Main methods: Flow cytometry was used to analyze the percentage of PD-1⁺ T cells, as well as the generation of ROS, GSH and GST in PD-1⁺ T cells. The expression of GST in the spleen and liver was analyzed by western blotting.

Key findings: The percentage of PD-1⁺ T cells was increased, but the ratio of GSH/GSSG was decreased in GVHD patients and the GVHD^high mouse model compared with that in the normal control group. hPMSCs downregulated the level of malondialdehyde (MDA) and upregulated the ratio of GSH/GSSG and the expression of glutathione S transferase (GST) in the plasma, spleen and liver of GVHD mice compared with those of PBS-treated GVHD mice. Further studies showed that the ROS level, as well as the expression of PD-1, in both CD3⁺ and CD4⁺ T cells from the spleen and liver of hPMSC-treated GVHD mice were decreased compared with those observed in PBS-treated mice.

Significance: hPMSCs downregulated ROS generation by increasing GSH and GST levels and further reduced the expression of PD-1 on T cells, thereby alleviating inflammation in GVHD mice.

Keywords: Glutathione (GSH); Glutathione S transferase (GST); Graft-versus-host disease (GVHD); Mesenchymal stromal cells (MSCs); Programmed death-1 (PD-1); Reactive oxygen species (ROS).