Comparison of the functional properties of murine dendritic cells generated in vivo with Flt3 ligand, GM-CSF and Flt3 ligand plus GM-CSF
Comparison of the functional properties of murine dendritic cells generated in vivo with Flt3 ligand, GM-CSF and Flt3 ligand plus GM-CSF
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DOI：
10.1006/cyto.2001.0995
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发表时间：
2002-02-07
期刊：
影响因子：
3.8
通讯作者：
McKenna, HJ
中科院分区：
文献类型：
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作者：
Daro, E;Butz, E;McKenna, HJ
Flt 3配体（FL）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）是树突状细胞（DC）的重要生长因子。在施用任一因子后，可以在体内产生大量的DC。我们试图扩展我们对这些细胞的功能特性的了解，包括它们引发幼稚CD 8（+）T细胞的能力。此外，我们比较了用单一细胞因子在体内产生的DC的性质与用FL+聚乙二醇修饰的GNI-CSF（pGM-CSF）的组合产生的DC的性质。FL+pGM-CSF处理产生的CD 11b（低）和CD 11b（高）DC的数量比单独使用任一种细胞因子都要多，并且这些DC在抗原（Ag）捕获方面更有效。FL+pGM-CSF产生的CD 11b（低）DC缺乏CD 8 α表达。在体内用LPS处理后，所有DC亚群上调CD 40、CD 80、CD 86和MHC II类表达，但令人惊讶的是Ag捕获未下调，并且一些DC亚群保留细胞内MHC H类囊泡的表达。因此，即使在用LPS体内活化后，DC仍保留未成熟DC的Ag捕获特性和成熟DC的Ag呈递/共刺激特性。尽管所有DC亚群刺激CD 4（+）T细胞增殖的效果相当，但FL产生的DC在引发Ag特异性CD 8（+）细胞溶解性T细胞方面比单独使用pGM-CSF或FL+pGM-CSF产生的DC更有效，并且CD 11b（高）DC在引发CD 8（+）T细胞方面比CD 11b（低）DC更有效。(C)2002 Elsevier Science Ltd.
Flt3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are important growth factors for dendritic cells (DC). Substantial numbers of DC can be generated in vivo following the administration of either factor. We sought to extend our knowledge of the functional properties of these cells including their ability to prime naive CD8(+) T cells. In addition, we compared the nature of the DC generated in vivo with the single cytokines to those generated with the combination of FL+polyethylene glycol-modified GNI-CSF (pGM-CSF). Treatment with FL+pGM-CSF yielded greater numbers of both CD11b(low) and CD11b(high) DC than with either cytokine alone, and these DC were more efficient at antigen (Ag) capture. The FL+pGM-CSF-generated CD11b(low) DC lacked expression of CD8alpha. Following treatment with LPS in vivo, all DC subsets upregulated CD40, CD80, CD86, and MHC class II expression, but surprisingly Ag capture was not downregulated and some DC subsets retained expression of intracellular MHC class H vesicles. Thus, even after activation in vivo with LPS, DC retained Ag capture properties of immature DC, and Ag presentation/costimulation properties of mature DC. Though all DC subsets stimulated CD4(+) T cell proliferation equivalently, FL-generated DC were more efficient at priming Ag-specific CD8(+) cytolytic T cells than DC generated with either pGM-CSF alone or FL+pGM-CSF, and CD11b(high) DC were more efficient at priming CD8(+) T cells than CD11b(low) DC. (C) 2002 Elsevier Science Ltd.