Gerber B O, Zanni M P, Uguccioni M, Loetscher M, Mackay C R, Pichler W J, Yawalkar N, Baggiolini M, Moser B
Theodor Kocher Institute, University of Bern, Switzerland.
Curr Biol. 1997 Nov 1;7(11):836-43. doi: 10.1016/s0960-9822(06)00371-x.
The chemokine eotaxin is produced at sites of allergic inflammation, binds selectively to the chemokine receptor CCR3 and attracts eosinophil and basophil leukocytes, which express high numbers of this receptor. Responses of T lymphocytes to eotaxin have not been reported so far. We have investigated the expression of CCR3 in T lymphocytes and analysed the properties and in vivo distribution of T lymphocytes expressing this receptor.
In search of chemokine receptors with selective expression in T lymphocytes, we have isolated multiple complementary DNAs (cDNAs) encoding CCR3 from a human CD4+ T-cell cDNA library. T-lymphocyte clones with selectivities for protein and non-protein antigens were analysed for expression of CCR3 and production of Th1- and Th2-type cytokines. Of 13 clones with surface CCR3, nine secreted enhanced levels of interleukin-4 and/or interleukin-5, indicating that CCR3 predominates in Th2-type lymphocytes. CCR3+ T lymphocytes readily migrated in response to eotaxin, and showed the characteristic changes in cytosolic free calcium. Immunostaining of contact dermatitis, nasal polyp and ulcerative colitis tissue showed that CCR3+ T lymphocytes are recruited together with eosinophils and, as assessed by flow cytometry, a large proportion of CD3+ cells extracted from the inflamed skin tissue were CCR3+. By contrast, CCR3+ T lymphocytes were absent from tissues that lack eosinophils, as demonstrated for normal skin and rheumatoid arthritis synovium.
We show that T lymphocytes co-localizing with eosinophils at sites of allergic inflammation express CCR3, suggesting that eotaxin/CCR3 represents a novel mechanism of T-lymphocyte recruitment. These cells are essential in allergic inflammation, as mice lacking mature T lymphocytes were insensitive to allergen challenge. Surface CCR3 may mark a subset of T lymphocytes that induce eosinophil mobilization and activation through local production of Th2-type cytokines.
趋化因子嗜酸性粒细胞趋化因子在变应性炎症部位产生，选择性地与趋化因子受体CCR3结合，并吸引表达大量该受体的嗜酸性粒细胞和嗜碱性粒细胞。目前尚未见T淋巴细胞对嗜酸性粒细胞趋化因子反应的报道。我们研究了CCR3在T淋巴细胞中的表达，并分析了表达该受体的T淋巴细胞的特性及体内分布。
为寻找在T淋巴细胞中选择性表达的趋化因子受体，我们从人CD4+T细胞cDNA文库中分离出多个编码CCR3的互补DNA（cDNA）。分析了对蛋白质和非蛋白质抗原有选择性的T淋巴细胞克隆的CCR3表达及Th1型和Th2型细胞因子的产生。在13个表面有CCR3的克隆中，9个分泌增强水平的白细胞介素-4和/或白细胞介素-5，表明CCR3在Th2型淋巴细胞中占主导。CCR3+T淋巴细胞对嗜酸性粒细胞趋化因子有反应时易于迁移，并显示出胞质游离钙的特征性变化。接触性皮炎、鼻息肉和溃疡性结肠炎组织的免疫染色显示，CCR3+T淋巴细胞与嗜酸性粒细胞一起被募集，且通过流式细胞术评估，从炎症皮肤组织中提取的大部分CD3+细胞为CCR3+。相比之下，缺乏嗜酸性粒细胞的组织中不存在CCR3+T淋巴细胞，如正常皮肤和类风湿性关节炎滑膜所证实。
我们发现，在变应性炎症部位与嗜酸性粒细胞共定位的T淋巴细胞表达CCR3，提示嗜酸性粒细胞趋化因子/CCR3代表了一种新的T淋巴细胞募集机制。这些细胞在变应性炎症中至关重要，因为缺乏成熟T淋巴细胞的小鼠对变应原攻击不敏感。表面CCR3可能标记了一部分T淋巴细胞，这些细胞通过局部产生Th2型细胞因子诱导嗜酸性粒细胞动员和活化。
