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与脐带血移植相关的耐受性可能取决于宿主树突状细胞的状态。

Tolerance associated with cord blood transplantation may depend on the state of host dendritic cells.

作者信息

Liu Enmei, Law Helen K W, Lau Yu-Lung

机构信息

Division of Respiratory Disorders, Children's Hospital, Chongqing University of Medical Sciences, Chongqing, China.

出版信息

Br J Haematol. 2004 Aug;126(4):517-26. doi: 10.1111/j.1365-2141.2004.05061.x.

Abstract

Allogeneic cord blood (CB) transplantation is associated with less severe graft-versus-host disease (GvHD), thought to be due to the immaturity of CB T cells, but how T cells interact with host and donor-derived dendritic cells (DCs) to initiate GvHD has not been elucidated. We therefore investigated the responses of CB and adult blood CD4(+) T cells co-cultured with adult host DCs of different maturities. Primed by adult host DCs, CB and adult blood CD4(+) T cells underwent similar changes in the expression of CD45RA/45RO, CD25, CD40L and CTLA-4. However, CB CD4(+) T cells, when primed by either immature or Bacillus Calmette-Guerin mycobacteria-treated adult host DCs, produced lower interferon-gamma (IFN-gamma) and higher interleukin-10 (IL-10), which is a regulatory T cell-like cytokine profile, as compared with adult blood CD4(+) T cells. In contrast, lipopolysaccharide (LPS)-treated adult host DCs significantly up-regulated IFN-gamma and down-regulated IL-10 production levels from CB CD4(+) T cells to that from adult blood CD4(+) T cells. The sustained low IFN-gamma and high IL-10 production from CB CD4(+) T cells co-cultured with adult blood DCs might account for the less severe GvHD occurrence after CB transplantation, which could be reversed by LPS-treated adult blood DCs.

摘要

异基因脐血(CB)移植与较轻微的移植物抗宿主病(GvHD)相关,一般认为这是由于脐血T细胞不成熟所致,但T细胞如何与宿主及供体来源的树突状细胞(DC)相互作用以引发GvHD尚未阐明。因此,我们研究了脐血和成人血液CD4(+) T细胞与不同成熟度的成人宿主DC共培养时的反应。在成人宿主DC的刺激下,脐血和成人血液CD4(+) T细胞在CD45RA/45RO、CD25、CD40L和CTLA-4的表达上发生了类似的变化。然而,当由未成熟或卡介苗处理的成人宿主DC刺激时,脐血CD4(+) T细胞产生的干扰素-γ(IFN-γ)较低,白细胞介素-10(IL-10)较高,这是一种调节性T细胞样的细胞因子谱,与成人血液CD4(+) T细胞相比。相反,脂多糖(LPS)处理的成人宿主DC显著上调了脐血CD4(+) T细胞中IFN-γ的产生水平,并下调了IL-10的产生水平,使其与成人血液CD4(+) T细胞的水平相当。与成人血液DC共培养的脐血CD4(+) T细胞持续产生低水平的IFN-γ和高水平的IL-10,这可能解释了脐血移植后GvHD发生较轻的原因,而LPS处理的成人血液DC可使其逆转。

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