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:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Thomson AW
Thomson AW
中科院分区:
其他
文献类型:
--
作者:
Zahorchak AF;Ezzelarab MB;Lu L;Turnquist HR;Thomson AW

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越来越多的来自小动物模型的证据表明,髓源性抑制细胞(MDSC)可以在抑制同种异体移植排斥反应和促进移植耐受中发挥关键作用。在这里,我们鉴定了正常恒河猴外周血中的CD 3 − CD 20 −HLA-DR− CD 14 + CD 33 + CD 11b+细胞。这些推定的单核细胞MDSC占lin−HLA-DR− PBMC的2.1 ± 1.7%。粒细胞-巨噬细胞集落刺激因子(GM-CSF)和粒细胞(G)-CSF的给药使其发生率增加至5.3 ± 3.4%。可从单个全恒河猴白细胞去除产物中流式分选的MDSC总数为38 ± 13.106(n=10只猴)。动员猴新鲜分离或冻存的MDSC加入抗CD 3 −和抗CD 28刺激的自体T细胞培养物中,可显著抑制CD 4+和CD 8 + T细胞增殖和细胞因子分泌(IFNγ、IL-17 A)。此外,这些MDSC增强了CD 4 + CD 25 hiFoxp 3+调节性T细胞(Treg)扩增,同时抑制活化的记忆T细胞的增殖并相对于效应细胞和终末分化的记忆T细胞增加Treg。精氨酸酶-1(Arg-1)的抑制,而不是诱导型一氧化氮合酶的活性,部分逆转了MDSC对CD 8 + T细胞增殖的抑制作用。因此,可以从NHP中分离功能性MDSC,用于在移植中作为治疗性细胞疫苗的前瞻性用途。
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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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:
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发表时间: 2010-11
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