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环磷酰胺诱导骨髓产生更高数量的前体树突状细胞,这些细胞能够在体内对 T 细胞进行功能性抗原呈递。

Cyclophosphamide induces bone marrow to yield higher numbers of precursor dendritic cells in vitro capable of functional antigen presentation to T cells in vivo.

机构信息

Surgery Department and Hollings Cancer Center, Medical University of South Carolina, Charleston, 29425, USA.

出版信息

Cell Immunol. 2010;261(2):134-43. doi: 10.1016/j.cellimm.2009.11.011. Epub 2009 Dec 5.

Abstract

We have shown recently that cyclophosphamide (CTX) treatment induced a marked increase in the numbers of immature dendritic cells (DCs) in blood, coinciding with enhanced antigen-specific responses of the adoptively transferred CD8(+) T cells. Because this DC expansion was preceded by DC proliferation in bone marrow (BM), we tested whether BM post CTX treatment can generate higher numbers of functional DCs. BM was harvested three days after treatment of C57BL/6 mice with PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from CTX-treated mice showed faster generation and yielded higher numbers of DCs with superior activation in response to toll-like receptor (TLR) agonists. Vaccination with peptide-pulsed DCs generated from BM from CTX-treated mice induced comparable adjuvant effects to those induced by control DCs. Taken together, post CTX BM harbors higher numbers of DC precursors capable of differentiating into functional DCs, which be targeted to create host microenvironment riches in activated DCs upon treatment with TLR agonists.

摘要

我们最近已经表明,环磷酰胺(CTX)治疗会导致血液中未成熟树突状细胞(DC)数量明显增加,同时增强了过继转移的 CD8(+) T 细胞的抗原特异性反应。由于这种 DC 扩增之前在骨髓(BM)中发生了 DC 增殖,我们测试了 CTX 治疗后 BM 是否可以产生更多数量的功能性 DC。在 PBS 或 CTX 处理 C57BL/6 小鼠 3 天后收获 BM,并在 GM-CSF/IL-4 体外培养。与对照组相比,CTX 处理组的 BM 显示出更快的生成速度,并产生了更多数量的 DC,对 Toll 样受体(TLR)激动剂的反应更优。用从 CTX 处理的 BM 产生的肽脉冲 DC 进行疫苗接种可诱导与对照 DC 诱导的相似的佐剂效应。总之,CTX 后 BM 含有更多的 DC 前体,能够分化为功能性 DC,这些前体可以在 TLR 激动剂治疗时靶向产生富含激活的 DC 的宿主微环境。

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