IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR3 and CCR4

IL-4-expressing bronchoalveolar T cells from asthmatic and healthy subjects preferentially express CCR3 and CCR4
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DOI:
10.1016/j.jaci.2005.03.052
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发表时间:
2005-09-01
影响因子:
14.2
通讯作者:
Wardlaw, AJ
Wardlaw, AJ
中科院分区:
医学1区
文献类型:
--
作者:
Morgan, AJ;Symon, FA;Wardlaw, AJ

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背景资料:T(H)1和T(H)2细胞趋化因子受体表达的极化的概念为它们向组织的差异募集提供了有吸引力的机制,这可以经受疾病特异性治疗干预。T(H)1细胞优先表达CXCR 3和CCR 5以及T(H)2细胞优先表达CCR 3、CCR 4和CCR 8的范例在体外极化细胞系的设置中已经很好地建立;然而,体内情况似乎不那么明确。目的:我们试图研究这种极化模式是否可以在人肺组织中证明。我们使用单细胞分析来研究哮喘患者外周血和支气管肺泡灌洗液T细胞上趋化因子受体表达和细胞因子产生之间的关系,哮喘是一种假定的T(H)2疾病,以及健康对照受试者。我们发现,在哮喘和对照受试者中,表达IL-4的血液和支气管肺泡灌洗液T细胞明显更可能表达T(H)2 2型趋化因子受体CCR 3和CCR 4,表达差异分别为10倍和2倍,结论:我们提供的证据表明,极化的T(H)2型趋化因子受体的IL-4表达细胞可以在体内设置,因此,这些细胞可能确实是敏感的差异模式的招聘作为结果的相关趋化因子在炎症部位的表达。
Background: The concept of the polarization of chemokine receptor expression by T(H)1 and T(H)2 cells provides an attractive mechanism for their differential recruitment to tissue, which could be subject to disease-specific therapeutic intervention. The paradigm that T(H)1 cells preferentially express CXCR3 and CCR5 and T(H)2 cells preferentially express CCR3, CCR4, and CCR8 has been well established in the setting of in vitro polarized cell lines; however, the situation in vivo appears less clear-cut.Objective: We sought to investigate whether this pattern of polarization can be demonstrated in human lung tissue.Methods: We used single-cell analysis to investigate the relationship between chemokine receptor expression and cytokine production on peripheral blood and bronchoalveolar lavage fluid T cells in patients with asthma, a putative T(H)2 disease, as well as in healthy control subjects.Results: We have found in both asthmatic and control subjects that IL-4-expressing blood and bronchoalveolar lavage fluid T cells are significantly more likely to express the T(H)2 type 2 chemokine receptors CCR3 and CCR4, with 10-fold and 2-fold differences in expression, respectively, compared with IFN-gamma-expressing cells.Conclusion: We have provided evidence that polarization of T(H)2-type chemokine receptors on IL-4-expressing cells can be demonstrated in an in vivo setting and therefore that these cells might indeed be susceptible to differential patterns of recruitment as a result of expression of the relevant chemokines at inflammatory sites.