In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid‐Derived Suppressor Cells. Issue 2 (15th September 2015)

• Record Type: Journal Article
• Authors: Zahorchak, A. F.; Ezzelarab, M. B.; Lu, L.; Turnquist, H. R.; Thomson, A. W.
• Is Part Of: American journal of transplantation. Volume 16:Issue 2(2016:Feb.)
• Page Start: 661
• Page End: 671
• Publication Date: 2015-09-15
• Subjects: basic (laboratory) research / science -- translational research / science -- immunosuppression / immune modulation -- immunobiology -- cellular biology -- animal models: nonhuman primate -- immune regulation -- cytokines / cytokine receptors; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13454
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : 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 × 10 6 (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 + CD25 hi Foxp3 + 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.