Background: CD11b⁺Ly6G^–Ly6C^high monocytic myeloid-derived suppressor cells (M-MDSCs) in mice can promote the apoptosis of T cells and induce regulatory T cells. Novel CD11b⁺CD11c⁺F4/80⁺ cells were previously reported and described as adipose tissue macrophages and renal mononuclear phagocytes, but not as an MDSC subset. The phenotypic and functional characteristics of CD11b⁺CD11c⁺F4/80⁺ as M-MDSCs remain unclear.

Aim: This study investigates the phenotype and immunosuppressive capability of murine CD11b⁺CD11c⁺F4/80⁺ M-MDSCs in vitro and in vivo.

Methods: CD11b⁺Ly6G^–Ly6C^high cells were isolated from the bone marrow of naïve BL/6 mice by negative selection and cultured with M-CSF, IL-4, TNF-a, and activated by lipopolysaccharide. The ability of M-MDSCs from WT mice, IL10 and NOS2 knockout (KO) mice to suppress CFSE-labeled T cells was assessed in vitro using a proliferation assay. For in vivo studies, we adoptively transferred syngeneic induced M-MDSCs to BL/6 recipients of DBA/2 heart allografts. The peripheral blood, spleen and graft were analyzed by flow cytometry and immunohistochemistry.

Result: Induced M-MDSCs showed a CD11b⁺CD11c⁺F4/80⁺Ly6C⁺ phenotype, also expressed iNOS, arginase, IDO, PD-L1, podoplanin, DC-SIGN, and they inhibited CD4⁺ T cell and CD8⁺ T cell proliferation both directly (cell-to-cell contact) and indirectly (transwell). Induced M-MDSCs from iNOS and IL-10 KO mice inhibited T cell proliferation as well as induced M-MDSCs from WT mice. Adoptive transfer of induced M-MDSCs resulted in increased CD4⁺Foxp3⁺ regulatory T cells in peripheral blood (15.7% vs 9.58%) and spleen (17.1% vs 9.85%) of treated vs untreated animals, respectively. We are currently pursuing the effect of these cells on allograft survival.

Conclusion: The CD11b⁺CD11c⁺F4/80⁺ M-MDSCs displayed a unique phenotype which is different from classical M1/M2 macrophages. These cells inhibited T cell proliferation in vitro and induced regulatory T cells in vivo.

CITATION INFORMATION: Jiang B, Aljabban I, Yang C, Ndishabandi D, White R, Russell P, Madsen J, Colvin R, Alessandrini A. The Phenotypic and Functional Characteristics of a Novel CD11b⁺CD11c⁺F4/80⁺ Monocytic Myeloid-Derived Suppressor Cell Subset. Am J Transplant. 2017;17 (suppl 3).

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