Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice

Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice
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DOI:
10.1182/blood.v99.6.2122
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发表时间:
2002-03-15
期刊:
影响因子:
20.3
通讯作者:
Shortman, K
Shortman, K
中科院分区:
医学1区
文献类型:
--
作者:
O'Keeffe, M;Hochrein, H;Shortman, K

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我们研究了多种细胞因子的给药的影响,包括后代脂蛋白-1(Progp-1),FLT-3配体(FL),颗粒细胞菌落刺激因子(G-CSF)和粒细胞 - 巨噬细胞刺激性刺激性刺激因子在小鼠脾脏中的树突状细胞(DC)种群上形式(PGM-CSF)。 POGP-1产生的总体直流数量最大,显然比其组成型FL和G-CSF组件更多。然而,直流数的扩展是强烈的选择性选择性的,pROGP-1和FL产生了CD8(+)DC的选择性扩展,而PGM-CSF产生了CD8( - )DC的选择性扩展。在鼠和人类重组制剂对鼠DC的影响之间观察到了令人惊讶的差异。 DC亚群的许​​多生物学功能由细胞因子扩展保持完整,包括ProgP-1和FL扩展的CD8(+)DC的能力产生T-helper-1偏见的细胞因子白介素12(IL-12)(IL-12) )。然而,除了G-CSF处理的小鼠以外的所有dcs扩展的DC在制造干扰素γ的能力上不足,并且用PGM-CSF治疗产生的CD8(+)DC具有废除形成生物活性IL-12的能力。 DC种群的这种选择性扩张及其细胞因子分泌能力的改变对在免疫调节中研究的细胞因子的临床使用具有影响。
We studied the effects of administration of several cytokines, including progenipoietin-1 (ProGP-1), Flt-3 ligand (FL), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor in a pegylated form (pGM-CSF), on dendritic cell (DC) populations in mouse spleen. ProGP-1 produced the most striking increase in overall DC numbers, apparently more than its constituent FL and G-CSF components. However, the expansion in DC numbers was strongly subpopulation selective, with ProGP-1 and FL producing selective expansion of CD8(+) DCs, whereas pGM-CSF produced selective expansion of CD8(-) DCs. Surprising differences were observed between the effects of murine and human recombinant FL preparations on murine DCs. Many of the biologic functions of the DC subpopulations expanded by cytokines remained intact, including the capacity of the ProGP-1- and FL-expanded CD8(+) DCs to produce the T-helper-1-biasing cytokine interleukin 12 (IL-12). However, the expanded DCs from all but G-CSF-treated mice were deficient in the ability to make interferon gamma, and the CD8(+) DCs produced with pGM-CSF treatment had an abrogated capacity to form bioactive IL-12. Such selective expansion of DC populations and alterations in their cytokine-secretion capacity have implications for clinical use of the studied cytokines in immune modulation.