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脐血树突状细胞可阻止初始T辅助细胞向Th1分化,无论其亚型如何。

Cord blood dendritic cells prevent the differentiation of naïve T-helper cells towards Th1 irrespective of their subtype.

作者信息

Naderi Nadereh, Pourfathollah Ali Akbar, Alimoghaddam Kamran, Moazzeni Seyed Mohammad

机构信息

Department of Immunology, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran.

出版信息

Clin Exp Med. 2009 Mar;9(1):29-36. doi: 10.1007/s10238-008-0020-2. Epub 2008 Nov 1.

Abstract

Allogeneic cord blood transplantation is associated with a less severe graft-versus-host disease (GVHD). This observation is thought to be due to immaturity of cord blood cell immune capabilities. Dendritic cells (DCs) are the most potent antigen-presenting cells of the immune system capable of initiation and regulation of immune responses. In this investigation, we hypothesized that non-manipulated cord blood dendritic cells (CBDCs) not only differ in their functional maturity from adult peripheral blood DCs (PBDCs) but also differ in their subsets and their preference in promoting Th1 or Th2 immune responses. Non-manipulated fresh DCs were isolated from cord blood (CB) and adult peripheral blood (PB) mononuclear cells as lineage marker negative cells. The differences in expression of costimulatory molecules, the proportion of myeloid and lymphoid DCs subsets, their immunostimulatory characteristics and their influence on promoting the differentiation of naïve T cells towards Th1 or Th2 cells were then investigated in these two populations. Our results showed that freshly isolated CBDCs, similar to cord blood monocyte derived DCs, were poor inducers of IFN-gamma secretion while they increased the induction of IL-4 production by T cells in comparison with PBDCs. CBDCs were also poor stimulators of allogenic T cells in mixed leukocyte reaction compared to adult peripheral blood dendritic cells. They also displayed decreased expression of HLA-DR and CD86 molecules. The ratio of lymphoid DCs (CD11c(-), CD123(+)) to myeloid DCs (CD11c(+), CD123(-)) was significantly higher in CB compared to PB. We conclude that CBDCs preferential priming of naive T cells towards Th2 population, seems to be an intrinsic property independent of their subtype. This property along with their functional immaturity should contribute to outcome of cord blood transplantation.

摘要

异基因脐血移植与较轻微的移植物抗宿主病(GVHD)相关。这一观察结果被认为是由于脐血细胞免疫能力不成熟所致。树突状细胞(DCs)是免疫系统中最强大的抗原呈递细胞,能够启动和调节免疫反应。在本研究中,我们假设未经处理的脐血树突状细胞(CBDCs)不仅在功能成熟度上与成人外周血DCs(PBDCs)不同,而且在其亚群以及促进Th1或Th2免疫反应的偏好方面也存在差异。从未经处理的新鲜DCs中分离出脐血(CB)和成人外周血(PB)单核细胞作为谱系标记阴性细胞。然后在这两个群体中研究共刺激分子表达的差异、髓样和淋巴样DCs亚群的比例、它们的免疫刺激特性以及它们对促进初始T细胞向Th1或Th2细胞分化的影响。我们的结果表明,与脐血单核细胞来源的DCs相似,新鲜分离的CBDCs诱导IFN-γ分泌的能力较差,而与PBDCs相比,它们能增加T细胞对IL-4产生的诱导。与成人外周血树突状细胞相比,CBDCs在混合淋巴细胞反应中对同种异体T细胞的刺激作用也较弱。它们还表现出HLA-DR和CD86分子表达的降低。与PB相比,CB中淋巴样DCs(CD11c(-),CD123(+))与髓样DCs(CD11c(+),CD123(-))的比例显著更高。我们得出结论,CBDCs将初始T细胞优先诱导为Th2群体,似乎是一种独立于其亚型的内在特性。这一特性连同其功能不成熟应有助于脐血移植的结果。

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