The Effect Of Hucmscs And Hcbmscs On T Lymphocyte Subsets

T lymphocytes are the effector cells of many autoimmune diseases.Studies have shown that mesenchymal stem cells can reduce the inappropriate immune response to avoid the ultra immune response by regulating the function of T lymphocyte.Now,injecting allochthonous MSCs has become the effective treatment of systemic lupus erythematosus,collagen induced arthritis and other autoimmune diseases.However,the mechanism of mesenchymal stem cells playing a role of immune regulation mechanism has not been fully revealed.In order to understand the immunoregulation capability of MSCs to T lymphocytes,firstly,we choose two competitive mesenchymal stem cells,umbilical cord mesenchymal stem cells(HUCMSCs)and human umbilical cord blood mesenchymal stem cells(HCBMSCs),no matter on source or ethics.We co-culture peripheral blood mononuclear cell(PBMCs)with HUCMSCs or HCBMSCs and detect the variation of T lymphocyte subsets.The results show that both HUCMSCs and HCBMSCs can affect the CD4+ and CD8+ T lymphocyte subsets.In details,both HUCMSCs and HCBMSCs can up-regulate CD4+CD25+FOXP3+ regulatory T cells,CD4+CD45RA-CCR7-effector memory T cells,CD8+CD45RA-CCR7-effector memory T cells and down regulate CD4+CD45RA+CCR7+ naive cells,CD8+CD45RA+CCR7+ naive cells,CD4+CD45RA-CCR7+ central memory T cells,CD8+CD45RA-CCR7+ central memory T cells.The results of flow cytometry and real-time PCR both indicate that with lastingness of co-culture,the immunoregulation effect of HUCMSCs and HCBMSCs become weak.Chimeric antigen receptor T-cell immunotherapy(CAR-T)is a cell therapy which makes T cells express chimeric antigen receptors to target particular tumor cells and kill tumor cells by genetic recombination.However,low preparation efficiency in vitro and low proliferation efficiency in vivo have become the important obstacles restricting the development of the CAR-T technology.Previous studies have shown that the percentage of naive cells and central memory T cells in the preparation of the CAR-T cells in vitro is proportional to the amplification efficiency of the CAR-T cells in vivo.Our studies above indicate that mesenchymal stem cells can regulate the proportion of different T lymphocyte subsets.Then we hope use mesenchymal stem cells to increase the proportion of naive cells and central memory T cells in CAR-T cells.In order to verify the hypothesis,we creatively co-cultures HUCMSCs or HCBMSCs with CD 19 CAR-T cells in vitro.The experimental results show that the number of lymphocytes has been maintained and the percentage of CD4+CD45RA+CCR7+ naive cells,CD8+CD45RA+CCR7+ naive cells,CD4+CD45RA-CCR7+ central memory T cells,CD8+CD45RA-CCR7+ central memory T cells has been increased.The existing literature reports that the percentage of naive cells and central memory T cells in the preparation of the CAR-T cells in vitro is proportional to the amplification efficiency of CAR-T cells in vivo.This means that in the preparation of CD 19 CAR-T cells in vitro,co-culturing the CD 19 CAR-T cells with HUCMSCs or HCBMSCs may be an effective method to solve the problem of low amplification efficiency of CD19 CAR-T cells in vivo.