The Study On The Mechanism Of HPMSCs Regulating PD-1~+T Cells Generation To Alleviate GVHD

Objective:To study that whether hPMSCs improve antioxidant capacity of T cells,regulate PD-1+T cells generation,and further alleviate GVHD,providing a new idea for the application of hPMSCs in GVHD treatment.Methods:6-8 week-old male C57BL/6 mice and female Balb/c mice were used to induce GVHD mouse model,and then hPMSCs or PBS were transplanted into mice at the peak of GVHD.The weight and clinical score were monitored daily.On 7 and 14 days after hPMSCs transplantation,the percent of spleen and liver CD3+PD-1+T and CD3+CD4+PD-1+T cells were detected by FCM,also the ROS,GSH and GST levels in spleen and liver CD3+PD-1+T and CD3+CD4+PD-1+T cells were analyzed by FCM.The malondialdehyde(MDA),GSH/GSSG ratio and GST in mice plasma,spleen and liver were detected on 7 days after hPMSCs transplantation.Results:The percent of CD3+PD-1+T and CD4+PD-1+T cells from spleen and liver were decreased in hPMSCs treated mice after 7 and 14 days hPMSCs transplantation,compared with PBS treated group(P<0.05).Compared with PBS group,the weight loss and clinical score were improved in mice receiving hPMSCs(P<0.01),also the inflammation and damage of lung,kidney and skin from hPMSCs treated mice were improved significantly compared with PBS group.The MDA levels in plasma,spleen and liver was decreased,while the GSH/GSSH ratio and GST expression were increased after treatment of hPMSCs,compared with PBS treatment group(P<0.05).The ROS levels in CD3+,CD4+T cells from spleen and liver were reduced in hPMSCs treated mice compared with PBS group on Day 7 and 14(P<0.01).When GVHD occurs,there was a significant positive correlation between the generation of ROS in T cells and the expression of PD-1 on T cells(P<0.01),and the ROS expression in PD-1-T cells was significantly lower than that in PD-1+T cells from mice spleen and liver(P<0.05).Moreover,both the GSH and GST content in PD-1+T cells within spleen and liver in hPMSCs group was higher than that in PBS group on Day 7 and Day 14(P<0.05).Conclusion:hPMSCs down-regulated ROS generation by increasing GSH and GST levels,and further reduced the percent of PD-1+T cells,in this way,alleviated inflammation in GVHD mice.