In VivoMobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid‐Derived Suppressor Cells

Increasing evidence from small animal models shows that myeloid‐derived suppressor cells (MDSCs) can play a crucial role in inhibiting allograft rejection and promoting transplant tolerance. We identified CD3−CD20−HLA‐DR−CD14+CD33+CD11b+cells in peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% ± 1.7% of lin−HLA‐DR−peripheral blood mononuclear cells. Administration of granulocyte‐macrophage colony‐stimulating factor (CSF) and granulocyte CSF increased their incidence to 5.3% ± 3.4%. The total number of MDSCs that could be flow sorted from a single whole rhesus leukapheresis product was 38 ± 13 × 106(n = 10 monkeys). Freshly isolated or cryopreserved MDSCs from mobilized monkeys incorporated in cultures of anti‐CD3– and anti‐CD28–stimulated autologous T cells markedly suppressed CD4+and CD8+T cell proliferation and cytokine secretion (interferon γ, IL‐17A). Moreover, these MDSCs enhanced CD4+CD25hiFoxp3+regulatory T cell (Treg) expansion while inhibiting proliferation of activated memory T cells and increasing Treg relative to effector and terminally differentiated memory T cells. Inhibition of arginase‐1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSCs on CD8+T cell proliferation. Consequently, functional MDSCs can be isolated from nonhuman primates for prospective use as therapeutic cellular vaccines in transplantation.