Memory T-cells and characterization of peripheral T-cell clones in acute Kawasaki disease.

Memory T-cells and characterization of peripheral T-cell clones in acute Kawasaki disease.
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DOI:
10.3109/08916930903405891
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发表时间:
2010-06
期刊:
影响因子:
3.5
通讯作者:
Burns JC
Burns JC
中科院分区:
医学4区
文献类型:
--
作者:
Franco A;Shimizu C;Tremoulet AH;Burns JC

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川崎是一种以免疫介导的动脉壁和心肌破坏为特征的小儿自限性血管炎。我们既不知道引发炎症的触发器,也不知道关闭炎症的开关。为了进一步了解KD发病机制和调节性T细胞在调节炎症反应中的作用,我们研究了6名KD受试者的循环效应记忆T细胞(CCR 7-和IL-15+ Tem)和中枢记忆T细胞(CCR 7+和IL-15+ Tcm)。在其中两个受试者中,我们通过有限稀释法克隆了剩余的T细胞群。在两名KD受试者中研究的Tem的TaqMan分析表明,Tem是促炎性CD 4 + T辅助1细胞和CD 8+细胞毒性T细胞。随着时间的推移,记忆T细胞,我们定义,循环Tem和Tcm是可检测的急性期在一些KD受试者治疗前静脉注射免疫球蛋白。Tem和Tcm在治疗2周内迅速扩张。循环的Tem池收缩,而Tcm在恢复期进一步增殖。在耗尽记忆T细胞后,从两名急性KD受试者衍生出许多T细胞克隆。这些T细胞中的绝大多数显示外周诱导的调节性T细胞(Treg)的功能表型。这些发现提供了深入了解KD适应性免疫应答的性质和动力学。
Kawasaki disease (KD) is a pediatric self-limited vasculitis characterized by immune-mediated destruction of the arterial wall and myocardium. Neither the trigger that incites the inflammation nor the switch that turns it off is known. To further our understanding of KD pathogenesis and the role of regulatory T-cells in modulating the inflammatory response, we studied circulating effector memory T-cells (CCR7− and IL-15+ Tem) and central memory T-cells (CCR7+ and IL-15+ Tcm) in six KD subjects. In two of the subjects, we cloned the remaining T-cell population by limiting dilution. TaqMan analysis of Tem studied in two KD subjects suggested that Tem are pro-inflammatory CD4+ T-helper 1 cells and CD8+ cytotoxic T-cells. Following memory T-cells over time, we defined that circulating Tem and Tcm are detectable during the acute phase in some KD subjects before treatment with intravenous immunoglobulin. Both Tem and Tcm expand rapidly within 2 weeks of treatment. The circulating Tem pool contracts, while Tcm further proliferate in the convalescent phase. Following depletion of memory T-cells, numerous T-cell clones were derived from two acute KD subjects. The large majority of these T-cells displayed the functional phenotype of peripherally induced regulatory T-cells (Treg). These findings provide insight into the nature and kinetics of the adaptive immune response in KD.
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