Toh Han C, Sun Li, Soe Yatanar, Wu Yonghui, Phoon Yee P, Chia Whay K, Wu Jeanie, Wong Kee Y, Tan Patrick
Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
Clin Immunol. 2009 Jul;132(1):83-92. doi: 10.1016/j.clim.2009.03.509. Epub 2009 Apr 2.
G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune tolerant profile with upregulation of genes related to Th2 and Treg cells, downregulation of genes associated with Th1 cells, cytotoxicity, antigen presentation and graft-versus-host disease (GVHD) and overexpression of negative regulators of Th17 differentiation. Immunophenotyping revealed that during G-CSF exposure donors had reduced levels of T cells with a Th17 phenotype (CD4+IL-17A+CCR6+IL-23R+), more than three times lower compared to normal controls. G-CSF also led to increased levels of CD4+CD25highCD45RO+ Treg cells. Furthermore, mRNA levels of RORgammat, a Th17-specific transcription factor, decreased in T cells isolated from G-CSF-mobilized PBSC harvests. Th17 cells have been implicated in autoimmune diseases and GVHD pathophysiology. Our study is the first to report the effect of G-CSF on the Th17 subpopulation.
粒细胞集落刺激因子(G-CSF)可在人体诱导功能性免疫耐受。在本研究中,通过基因表达谱分析和免疫表型分析对来自G-CSF动员的外周血干细胞(PBSC)供体的纯化T细胞进行了分析。结果显示主要呈现免疫耐受特征,与Th2和调节性T细胞(Treg)相关的基因上调,与Th1细胞、细胞毒性、抗原呈递和移植物抗宿主病(GVHD)相关的基因下调,以及Th17分化的负调节因子过表达。免疫表型分析显示,在G-CSF暴露期间,供体具有Th17表型(CD4+IL-17A+CCR6+IL-23R+)的T细胞水平降低,与正常对照相比降低了三倍多。G-CSF还导致CD4+CD25highCD45RO+ Treg细胞水平升高。此外,从G-CSF动员的PBSC采集中分离的T细胞中,Th17特异性转录因子维甲酸相关孤儿受体γt(RORγt)的mRNA水平降低。Th17细胞与自身免疫性疾病和GVHD病理生理学有关。我们的研究首次报道了G-CSF对Th17亚群的影响。