Pulendran B, Banchereau J, Burkeholder S, Kraus E, Guinet E, Chalouni C, Caron D, Maliszewski C, Davoust J, Fay J, Palucka K
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
J Immunol. 2000 Jul 1;165(1):566-72. doi: 10.4049/jimmunol.165.1.566.
Dendritic cells (DCs) have a unique ability to stimulate naive T cells. Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and in vivo. In humans, the monocyte-derived CD11c+ DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11c- plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines. In this paper we report that administration of either Flt3-ligand (FL) or G-CSF to healthy human volunteers dramatically increases distinct DC subsets, or DC precursors, in the blood. FL increases both the CD11c+ DC subset (48-fold) and the CD11c- IL-3R+ DC precursors (13-fold). In contrast, G-CSF only increases the CD11c- precursors (>7-fold). Freshly sorted CD11c+ but not CD11c- cells stimulate CD4+ T cells in an allogeneic MLR, whereas only the CD11c- cells can be induced to secrete high levels of IFN-alpha, in response to influenza virus. CD11c+ and CD11c- cells can mature in vitro with GM-CSF + TNF-alpha or with IL-3 + CD40 ligand, respectively. These two subsets up-regulate MHC class II costimulatory molecules as well as the DC maturation marker DC-lysosome-associated membrane protein, and they stimulate naive, allogeneic CD4+ T cells efficiently. These two DC subsets elicit distinct cytokine profiles in CD4+ T cells, with the CD11c- subset inducing higher levels of the Th2 cytokine IL-10. The differential mobilization of distinct DC subsets or DC precursors by in vivo administration of FL and G-CSF offers a novel strategy to manipulate immune responses in humans.
树突状细胞（DCs）具有刺激初始T细胞的独特能力。最近的证据表明，不同的DC亚群在体外和体内可引导不同类型的免疫反应。在人类中，单核细胞来源的CD11c⁺ DCs在体外诱导T细胞产生Th1细胞因子，而CD11c⁻浆细胞样T细胞来源的DCs引发Th2细胞因子的产生。在本文中，我们报告向健康人类志愿者施用Flt3配体（FL）或粒细胞集落刺激因子（G-CSF）可显著增加血液中不同的DC亚群或DC前体细胞。FL可增加CD11c⁺ DC亚群（48倍）和CD11c⁻ IL-3R⁺ DC前体细胞（13倍）。相比之下，G-CSF仅增加CD11c⁻前体细胞（>7倍）。新鲜分选的CD11c⁺细胞而非CD11c⁻细胞在同种异体混合淋巴细胞反应（MLR）中刺激CD4⁺ T细胞，而只有CD11c⁻细胞在受到流感病毒刺激时可被诱导分泌高水平的干扰素-α。CD11c⁺和CD11c⁻细胞可分别在体外与粒细胞-巨噬细胞集落刺激因子（GM-CSF）+肿瘤坏死因子-α（TNF-α）或与白细胞介素-3（IL-3）+ CD40配体一起成熟。这两个亚群上调MHC II类共刺激分子以及DC成熟标志物DC-溶酶体相关膜蛋白，并且它们有效地刺激初始的同种异体CD4⁺ T细胞。这两个DC亚群在CD4⁺ T细胞中引发不同的细胞因子谱，其中CD11c⁻亚群诱导更高水平的Th2细胞因子白细胞介素-10（IL-10）。通过体内施用FL和G-CSF对不同DC亚群或DC前体细胞进行差异性动员，为调控人类免疫反应提供了一种新策略。
