*Purpose: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population that have the ability to cause immunosuppression. In recent years, MDSCs have attracted attention as a therapeutic target in treating cancer, inflammation, and transplantation. There are two subsets of MDSCs, monocytic MDSCs (Mo-MDSCs: CD11b+Ly-6G-Ly-6Chi) and polymorphonuclear MDSCs (PMN-MDSCs: CD11b+Ly-6G+Ly-6Clow), and many studies have reported their roles in immunosuppression. MDSCs can be cultured from bone marrow (BM) cells in vitro using cytokines. We analyzed the impact of BM-derived MDSCs on a murine heart transplantation model and compared the effects of MDSC subsets.

*Methods: BM-MDSCs were cultured with interleukin (IL)-6 and/or granulocyte-macrophage colony-stimulating factor (GM-CSF), and their ability to suppress T cell activation and affect graft survival in a murine heart transplantation model were analyzed. In addition, Mo- and PMN-MDSCs were sorted from BM-MDSCs, and their effects were compared.

*Results: The combination of GM-CSF and IL-6 promoted the growth of Mo-MDSCs with high inducible nitric oxide synthase (iNOS) and arginase 1 expression. BM-MDSCs inhibited T cell proliferation via iNOS and expanded T regulatory cells in vitro. In vivo, BM-MDSCs contributed to prolonged graft survival. Comparing the phenotypes, Mo-MDSCs had a stronger immunosuppressive capacity than PMN-MDSCs and contributed to prolonged graft survival

*Conclusions: These results highlight that inducing Mo-MDSCs is an important therapeutic goal when using MDSCs to treat solid tissue transplantation.

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