In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells.
In Vivo Mobilization and Functional Characterization of Nonhuman Primate Monocytic Myeloid-Derived Suppressor Cells.
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DOI:
10.1111/ajt.13454
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发表时间:
2016-02
期刊:
影响因子:
--
通讯作者:
Thomson AW
中科院分区:
文献类型:
--
作者:
Zahorchak AF;Ezzelarab MB;Lu L;Turnquist HR;Thomson AW
There is growing evidence from small animal models that myeloid-derived suppressor cells (MDSC) can play a crucial role in inhibiting allograft rejection and in promoting transplant tolerance. Here, we identified CD3−CD20−HLA-DR−CD14+CD33+CD11b+ cells in peripheral blood of normal rhesus macaques. These putative, monocytic MDSC constituted 2.1 ± 1.7% of lin−HLA-DR− PBMC. Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF increased their incidence to 5.3 ± 3.4%. The total number of MDSC that could be flow-sorted from a single whole rhesus leukapheresis product was 38 ± 13.106 (n=10 monkeys). Freshly-isolated or cryopreserved MDSC 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 (IFNγ, IL-17A). Moreover, these MDSC 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 (Arg-1), but not inducible nitric oxide synthase activity, partially reversed the inhibitory effect of the MDSC on CD8+ T cell proliferation. Thus, functional MDSC can be isolated from NHP for prospective use as therapeutic cellular vaccines in transplantation.
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影响因子:
5.6
作者:
Greten TF;Manns MP;Korangy F
通讯作者:
Korangy F
影响因子:
4.4
作者:
Dilek, Nahzli;Poirier, Nicolas;Vanhove, Bernard
通讯作者:
Vanhove, Bernard
影响因子:
20.3
作者:
Highfill, Steven L.;Rodriguez, Paulo C.;Blazar, Bruce R.
通讯作者:
Blazar, Bruce R.
DOI:
10.1111/ajt.12310
发表时间:
2013-08
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
作者:
Ezzelarab MB;Zahorchak AF;Lu L;Morelli AE;Chalasani G;Demetris AJ;Lakkis FG;Wijkstrom M;Murase N;Humar A;Shapiro R;Cooper DK;Thomson AW
通讯作者:
Thomson AW
影响因子:
2.7
作者:
Boros, Peter;Ochando, Jordi C.;Chen, Shu-Hsia;Bromberg, Jonathan S.
通讯作者:
Bromberg, Jonathan S.