CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo.

CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo.
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DOI:
10.1084/jem.191.2.265
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发表时间:
2000-01-17
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Gutierrez-Ramos JC
Gutierrez-Ramos JC
中科院分区:
其他
文献类型:
--
作者:
Lloyd CM;Delaney T;Nguyen T;Tian J;Martinez-A C;Coyle AJ;Gutierrez-Ramos JC

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过敏者外周血分离的CD4细胞体外扩增后表达CC趋化因子受体(CCR)3和CCR4。此外,在体外极化的人类辅助性T细胞2型(Th2)在某些激活/分化阶段选择性地表达CCR3和CCR4,并优先对配体嗜酸性粒细胞趋化因子和单核细胞衍生趋化因子(MDC)作出反应。然而,当讨论这种不同表达的体内意义时,就会出现争议。为了阐明CCR3/eoaxin和CCR4/MDC在Th2细胞体内募集中的功能作用,我们将效应Th细胞转移到幼鼠体内,以诱导过敏性呼吸道疾病。反复抗原攻击后对这些细胞的跟踪证实,CCR3/eoaxin和CCR4/MDC轴都有助于Th2细胞向肺内的募集,证明了这些受体在体内的表达与Th2细胞的相关性。我们已经证明,CCR3/eoaxin途径的参与仅限于体内反应的早期阶段,而重复的抗原刺激导致CCR4/MDC途径的主要使用。我们认为,效应Th2细胞最初对CCR3/eoaxin和CCR4/MDC途径都有反应,但CCR4阳性细胞的逐渐增加导致了CCR4/MDC轴在体内Th2细胞的长期募集中占据优势。
Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.
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影响因子: --
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