In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells

• DOI: 10.1111/ajt.13454
• Publication Date: 2015-09-15T20:47:55Z
• Authors: A.F. Zahorchak; M.B. Ezzelarab; L. Lu; H.R. Turnquist; A.W. Thomson
• Keywords: Myeloid-derived Suppressor Cell

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(+) peripheral blood of healthy rhesus macaques. These putative monocytic MDSCs constituted 2.1% ± 1.7% lin(-)HLA-DR(-) mononuclear cells. Administration granulocyte-macrophage colony-stimulating factor (CSF) granulocyte CSF increased their incidence to 5.3% 3.4%. The total number could be flow sorted single whole leukapheresis product was 38 13 × 10(6) (n = 10 monkeys). Freshly isolated or cryopreserved mobilized monkeys incorporated cultures anti-CD3- anti-CD28-stimulated autologous T markedly suppressed CD4(+) CD8(+) cell proliferation cytokine secretion (interferon γ, IL-17A). Moreover, these enhanced CD4(+)CD25(hi)Foxp3(+) regulatory (Treg) expansion while activated memory increasing Treg relative effector terminally differentiated Inhibition arginase-1, but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect on proliferation. Consequently, functional nonhuman primates for prospective use as therapeutic cellular vaccines transplantation.