Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
J Immunol. 2012 Apr 15;188(8):3603-10. doi: 10.4049/jimmunol.1102741. Epub 2012 Mar 21.
Monocytes can differentiate into various cell types with unique specializations depending on their environment. Under certain inflammatory conditions, monocytes upregulate expression of the dendritic cell marker CD11c together with MHC and costimulatory molecules. These phenotypic changes indicate monocyte differentiation into a specialized subset of dendritic cells (DCs), often referred to as monocyte-derived DCs or inflammatory DCs (iDCs), considered important mediators of immune responses under inflammatory conditions triggered by infection or vaccination. To characterize the relative contribution of cDCs and iDCs under conditions that induce strong immunity to coadministered Ags, we analyzed the behavior of spleen monocytes in response to anti-CD40 treatment. We found that under sterile inflammation in mice triggered by CD40 ligation, spleen monocytes can rapidly and uniformly exhibit signs of activation, including a surface phenotype typically associated with their conversion into DCs. These inflammatory monocytes remain closely related to their monocytic lineage, preserving expression of CD115, scavenging function, tissue distribution and poor capacity for Ag presentation characteristic of their monocyte precursors. In addition, 3-4 d after delivery of the inflammatory stimuli, these cells reverted to a monocyte-associated phenotype typical of the steady state. These findings indicate that, in response to anti-CD40 treatment, spleen monocytes are activated and express certain DC surface markers without acquiring functional characteristics associated with DCs.
单核细胞可以根据其所处的环境分化为具有独特功能专业化的各种细胞类型。在某些炎症条件下,单核细胞上调树突状细胞标志物 CD11c 的表达,同时还表达 MHC 和共刺激分子。这些表型变化表明单核细胞分化为一种特殊的树突状细胞亚群(DCs),通常称为单核细胞衍生的 DC 或炎性 DC(iDCs),被认为是感染或疫苗接种引发炎症条件下免疫反应的重要介质。为了在诱导对共施用抗原产生强烈免疫的条件下描述 cDCs 和 iDCs 的相对贡献,我们分析了脾脏单核细胞对抗 CD40 治疗的反应。我们发现,在 CD40 配体引发的无菌性炎症小鼠中,脾脏单核细胞可以迅速而均匀地表现出活化的迹象,包括与它们转化为 DC 相关的表面表型。这些炎性单核细胞仍然与其单核细胞谱系密切相关,保持表达 CD115、吞噬功能、组织分布和其单核细胞前体特征的低抗原呈递能力。此外,在给予炎症刺激后 3-4 天,这些细胞恢复到与稳态相关的典型单核细胞相关表型。这些发现表明,在抗 CD40 治疗的作用下,脾脏单核细胞被激活并表达某些 DC 表面标志物,而不获得与 DC 相关的功能特征。