Willimann K, Legler D F, Loetscher M, Roos R S, Delgado M B, Clark-Lewis I, Baggiolini M, Moser B
Theodor-Kocher Institute, University of Bern, Switzerland.
Eur J Immunol. 1998 Jun;28(6):2025-34. doi: 10.1002/(SICI)1521-4141(199806)28:06<2025::AID-IMMU2025>3.0.CO;2-C.
Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a novel CC chemokine with selectivity for T lymphocytes and preferential expression in lymphoid tissues. We have studied its production, receptor usage and biological activities. High levels of SLC mRNA were detected in lymph nodes, the gastrointestinal tract and several gland tissues, but no expression was found by Northern blot analysis in freshly isolated or stimulated blood monocytes and lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed constitutive expression of SLC in the T cell areas and the marginal zone of follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B cell areas or sinuses. Comparison with immunocytochemical staining showed similarity between the in situ expression of SLC and the distribution of interdigitating dendritic cells but not with sinus-lining dendritic cells, macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its activity increased considerably when the cells were conditioned with IL-2 or phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also induced Ca2+ mobilization in these cells. Similar responses were obtained with EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7. This was confirmed using murine pre-B cells stably transfected with CCR7 which bound SLC with high affinity and showed chemotaxis and Ca2+ mobilization in response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A maximum was reached in 2-3 days and expression returned to initial levels within 8-10 days. The present study shows that SLC is constitutively produced within the T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.
二级淋巴组织趋化因子（SLC），也被称为外渗素-2和6Ckine，是一种新型CC趋化因子，对T淋巴细胞具有选择性，并在淋巴组织中优先表达。我们研究了它的产生、受体使用情况和生物学活性。在淋巴结、胃肠道和几种腺体组织中检测到高水平的SLC mRNA，但通过Northern印迹分析在新鲜分离或刺激的血液单核细胞、淋巴细胞、中性粒细胞和嗜酸性粒细胞中未发现表达。原位杂交显示SLC在淋巴结和黏膜相关淋巴组织的T细胞区以及滤泡边缘区有组成性表达，但在B细胞区或窦中无表达。与免疫细胞化学染色比较显示，SLC的原位表达与交错突细胞的分布相似，但与衬里窦的树突状细胞、巨噬细胞或T淋巴细胞不同。SLC诱导T淋巴细胞趋化，当细胞用白细胞介素-2（IL-2）或植物血凝素（PHA）处理时，其活性显著增加。在最佳条件下，SLC具有异常高的效力，可诱导高达50%的输入T淋巴细胞迁移。SLC还能诱导这些细胞中的钙离子动员。用EBI1配体趋化因子（ELC）也获得了类似的反应，两种趋化因子的顺序刺激导致交叉脱敏，表明SLC通过ELC受体CCR7起作用。这一点通过稳定转染CCR7的小鼠前B细胞得到证实，该细胞以高亲和力结合SLC，并对SLC和ELC表现出趋化和钙离子动员。在T淋巴细胞中，增强趋化反应性的PHA和IL-2也显著增强CCR7表达。与所有已知的趋化因子受体不同，IL-2对CCR7的上调是短暂的。在2 - 3天达到最大值，8 - 10天内表达恢复到初始水平。本研究表明，SLC在二级淋巴器官的T细胞区内组成性产生，并通过CCR7吸引T淋巴细胞。
