Expansion and activation kinetics of immune cells during early phase of GVHD in mouse model based on chemotherapy conditioning.

Expansion and activation kinetics of immune cells during early phase of GVHD in mouse model based on chemotherapy conditioning.
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DOI:
10.1155/2010/142943
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发表时间:
2010
影响因子:
--
通讯作者:
Hassan M
Hassan M
中科院分区:
其他
文献类型:
--
作者:
Sadeghi B;Al-Hashmi S;Hassan Z;Rozell B;Concha H;Lundmark C;Grönvik KO;Abedi-Valugerdi M;Hassan M

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在本文中,我们已经调查了早期的病理生理事件,移植物抗宿主病(GVHD),造血干细胞移植(HSCT)的主要并发症。用白消安/环磷酰胺(Bu-Cy)处理的BLLB/c雌性小鼠移植同种异体雄性C57 BL/6。对照组为同系移植Balb/c小鼠。在同种异体环境中,与同基因HSCT相比,在第+3天观察到供体树突状细胞(DC)的显著扩增和成熟,而供体T细胞CD 8+在第+5天增加(230%)。在第+5天,炎性细胞因子IL-2、IFN-γ和TNF-α的最高水平与T细胞活化相匹配。伴随着幼稚T细胞获得效应记忆表型,并从脾脏迁移到外周淋巴器官。因此,在Bu-Cy预处理供体后的GHVD的非常早期阶段,DC在供体T细胞的活化中起重要作用。随后,供体幼稚T细胞获得效应记忆表型并启动GVHD。
In the present paper, we have investigated early pathophysiological events in graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell transplantation (HSCT). BLLB/c female mice conditioned with busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6. Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic settings, significant expansion and maturation of donor dendritic cells (DCs) were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%) compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN-gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naïve T-cells gain effecr-memory phenotype and migrated from spleen to peripheral lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy conditioning donor, DCs play an important role in the activation of donor T cells. Subsequently, donor naïve T-cells gain effector-memory phenotype and initiate GVHD.
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