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体外扩增的脐血 CD4 T 淋巴细胞与外周血来源的 CD4 T 淋巴细胞相比,其细胞因子相关基因的表达谱明显不同。

Ex vivo expanded cord blood CD4 T lymphocytes exhibit a distinct expression profile of cytokine-related genes from those of peripheral blood origin.

机构信息

Department of Developmental Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan.

出版信息

Immunology. 2009 Nov;128(3):405-19. doi: 10.1111/j.1365-2567.2009.03122.x.

Abstract

With an increase in the importance of umbilical cord blood (CB) as an alternative source of haematopoietic progenitors for allogenic transplantation, donor lymphocyte infusion (DLI) with donor CB-derived activated CD4(+) T cells in the unrelated CB transplantation setting is expected to be of increased usefulness as a direct approach for improving post-transplant immune function. To clarify the characteristics of activated CD4(+) T cells derived from CB, we investigated their mRNA expression profiles and compared them with those of peripheral blood (PB)-derived activated CD4(+) T cells. Based on the results of a DNA microarray analysis and quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), a relatively high level of forkhead box protein 3 (Foxp3) gene expression and a relatively low level of interleukin (IL)-17 gene expression were revealed to be significant features of the gene expression profile of CB-derived activated CD4(+) T cells. Flow cytometric analysis further revealed protein expression of Foxp3 in a portion of CB-derived activated CD4(+) T cells. The low level of retinoic acid receptor-related orphan receptor gamma isoform t (RORgamma t) gene expression in CB-derived activated CD4(+) T cells was speculated to be responsible for the low level of IL-17 gene expression. Our data indicate a difference in gene expression between CD4(+) T cells from CB and those from PB. The findings of Foxp3 expression, a characteristic of regulatory T cells, and a low level of IL-17 gene expression suggest that CB-derived CD4(+) T cells may be a more appropriate source for DLI.

摘要

随着脐带血 (CB) 作为异体移植造血祖细胞替代来源的重要性增加,在无关 CB 移植背景下,使用供者 CB 来源的激活 CD4(+) T 细胞进行供者淋巴细胞输注 (DLI),有望作为一种直接改善移植后免疫功能的方法变得更加有用。为了阐明 CB 来源的激活 CD4(+) T 细胞的特征,我们研究了它们的 mRNA 表达谱,并将其与外周血 (PB) 来源的激活 CD4(+) T 细胞进行了比较。基于 DNA 微阵列分析和定量实时逆转录聚合酶链反应 (RT-PCR) 的结果,发现 Foxp3 基因表达水平相对较高和白细胞介素 (IL)-17 基因表达水平相对较低是 CB 来源的激活 CD4(+) T 细胞基因表达谱的显著特征。流式细胞术分析进一步显示 CB 来源的激活 CD4(+) T 细胞中 Foxp3 蛋白的表达。推测 CB 来源的激活 CD4(+) T 细胞中视黄酸受体相关孤儿受体 γ 同种型 t (RORgamma t) 基因表达水平较低是导致 IL-17 基因表达水平较低的原因。我们的数据表明 CB 来源的 CD4(+) T 细胞与 PB 来源的 CD4(+) T 细胞之间存在基因表达差异。Foxp3 表达的发现,即调节性 T 细胞的特征,以及 IL-17 基因表达水平较低表明,CB 来源的 CD4(+) T 细胞可能是 DLI 的更合适来源。

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