Myeloid-derived suppressor cells (MDSCs) consist of heterogeneous myeloid progenitors and precursors that was first defined in cancer patients and are characterized by a regulatory ability to inhibit T cells responses. A growing body of knowledge indicates the potential involvement of monocytic myeloid-derived suppressor cells (M-MDSCs) in transplantation. As the most commonly used induction regimen, rabbit anti-thymocyte globulin (rATG) exerts a great influence on T cells and NK cells, however, its effect on M-MDSCs remains ambiguous. We herein reported, compared with patients without rATG induction, circulating CD11b⁺CD33^highHLA-DR^–CD14⁺CD15^– M-MDSCs in rATG group increase significantly within the first month after transplantation, then restored to the preoperative levels(Fig1). The isolated M-MDSCs effectively inhibited CD3/CD28-stimulated T cells proliferation in vitro(Fig2) . The accumulation of functional M-MDSCs could be associated with the sharp elevation of IFN-γ and IL6 in plasma. To demonstrate the hypothesis, we managed to induce M-MDSCs in vitro by culturing purified monocytes from healthy donors with/without the presence of IFN-γ/IL6. Compared with GM-CSF alone, GM-CSF+ IFN-γ/IL6 remarkably down-regulated HLA-DR expression on monocytes, resembling the phenotypes of circulating M-MDSCs. In the function assay, GM-CSF+ IFN-γ/IL6-induced M-MDSCs showed a stronger ability to suppress CD4⁺ and CD8⁺ T cells proliferation in vitro. In summary, rATG would significantly induce functional M-MDSCs in kidney transplantation recipients in IFN-γ/IL6-depended manner. Further investigation with humanized animal models are needed to verify the clinical observation.

CITATION INFORMATION: Jiang Y., Zhang X. Effect of rATG on Monocytic Myeloid-Derived Suppressor Cells and Its Associated Mechanisms in Kidney Transplantation Recipients Am J Transplant. 2017;17 (suppl 3).

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