Therapeutic potential of monocytic MDSCs from peripheral blood monocytes in transplant rejection

Abstract

Myeloid-derived suppressor cells (MDSCs) were initially found to contribute to immunosuppression in tumor patients and have recently been recognized as a subset of innate immune cells. They are a heterogeneous population composed of monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs). In addition, MDSCs have been reported to induce immunological tolerance and prolong the graft survival in transplantation. In mouse CD11b + Gr-1 + cells, MDSCs have been reported to exhibit immunosuppressive functions under various inflammatory conditions. On the other hand, human MDSCs do not have a universal marker and have not been well defined. Furthermore, while mouse CD11b + Gr-1 + MDSCs account for 20-30% of bone marrow cells, human peripheral blood includes only a few percent of MDSCs. Hence, further investigations of human MDSCs and the development of strategies for isolating human MDSCs are mandatory for their use in the clinic for transplantation. We previously established a new strategy to generate monocytic MDSCs in vitro and to isolate them from human peripheral blood mononuclear cells (PBMC). Based on these studies, we have concluded that they have great potential for suppressing cytotoxic T lymphocyte (CTL)-mediated xenocytotoxicity and NK-mediated xenocytotoxicity. Furthermore, they also suppress macrophage-mediated xenocytotoxicity significantly. Here, we review the therapeutic potential of MDSCs in transplantation.