O'Keeffe Meredith, Hochrein Hubertus, Vremec David, Pooley Joanne, Evans Robert, Woulfe Susan, Shortman Ken
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria 3050, Australia.
Blood. 2002 Mar 15;99(6):2122-30. doi: 10.1182/blood.v99.6.2122.
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.
我们研究了几种细胞因子，包括祖细胞生成素-1（ProGP-1）、Flt-3配体（FL）、粒细胞集落刺激因子（G-CSF）和聚乙二醇化形式的粒细胞-巨噬细胞集落刺激因子（pGM-CSF）对小鼠脾脏中树突状细胞（DC）群体的影响。ProGP-1使DC总数出现了最显著的增加，显然超过了其组成成分FL和G-CSF。然而，DC数量的增加具有强烈的亚群选择性，ProGP-1和FL能选择性地扩增CD8⁺ DC，而pGM-CSF能选择性地扩增CD8⁻ DC。在小鼠和人重组FL制剂对小鼠DC的作用之间观察到了惊人的差异。细胞因子扩增的DC亚群的许多生物学功能仍然完好，包括ProGP-1和FL扩增的CD8⁺ DC产生偏向于辅助性T细胞1的细胞因子白细胞介素12（IL-12）的能力。然而，除G-CSF处理的小鼠外，所有小鼠扩增的DC产生干扰素γ的能力都不足，并且pGM-CSF处理产生的CD8⁺ DC形成生物活性IL-12的能力被消除。DC群体的这种选择性扩增及其细胞因子分泌能力的改变对所研究的细胞因子在免疫调节中的临床应用具有重要意义。
