Stanford Marianne M, Issekutz Thomas B
Departments of Microbiology & Immunology, Dalhousie University Avenue, Halifax, Nova Scotia, Canada.
J Leukoc Biol. 2003 Nov;74(5):791-9. doi: 10.1189/jlb.1102547. Epub 2003 Aug 1.
In chronic inflammatory reactions such as rheumatoid arthritis and multiple sclerosis, T cells in the inflamed tissue express the chemokine receptors CXCR3 and CCR5, and the chemokine ligands (CCL) of these receptors are present in the inflammatory lesions. However, the contribution of these chemokines to T cell recruitment to sites of inflammation is unclear. In addition, the relative roles of the chemokines that bind CXCR3 (CXCL9, CXCL10, CXCL11) and CCR5 (CCL3, CCL4, CCL5) in this process are unknown. The in vitro chemotaxis and in vivo migration of antigen-activated T lymphoblasts and unactivated spleen T cells to chemokines were examined. T lymphoblasts migrated in vitro to CXCR3 ligands with a relative potency of CXCL10 > CXCL11 > CXCL9, but these cells demonstrated much less chemotaxis to the CCR5 ligands. In vivo, T lymphocytes were recruited in large numbers with rapid kinetics to skin sites injected with CXCL10 and CCL5 and less to CCL3, CCL4, CXCL9, and CXCL11. The combination of CCL5 with CXCL10 but not the other chemokines markedly increased recruitment. Coinjection of interferon-gamma, tumor necrosis factor alpha, and interleukin-1alpha to up-regulate endothelial cell adhesion molecule expression with CXCL10 or CCL5 induced an additive increase in lymphoblast migration. Thus, CXCR3 ligands are more chemotactic than CCR5 ligands in vitro; however, in vivo, CXCL10 and CCL5 have comparable T cell-recruiting activities to cutaneous sites and are more potent than the other CXCR3 and CCR5 chemokines. Therefore, in vitro chemotaxis induced by these chemokines is not necessarily predictive of their in vivo lymphocyte-recruiting activity.
在类风湿性关节炎和多发性硬化症等慢性炎症反应中，炎症组织中的T细胞表达趋化因子受体CXCR3和CCR5，且这些受体的趋化因子配体（CCL）存在于炎症病变中。然而，这些趋化因子对T细胞募集到炎症部位的作用尚不清楚。此外，在此过程中，与CXCR3结合的趋化因子（CXCL9、CXCL10、CXCL11）和与CCR5结合的趋化因子（CCL3、CCL4、CCL5）的相对作用也未知。研究人员检测了抗原激活的T淋巴母细胞和未激活的脾脏T细胞对趋化因子的体外趋化性和体内迁移情况。T淋巴母细胞在体外对CXCR3配体的迁移能力相对强弱为CXCL10 > CXCL11 > CXCL9，但这些细胞对CCR5配体的趋化性要低得多。在体内，T淋巴细胞大量快速地募集到注射了CXCL10和CCL5的皮肤部位，而对CCL3、CCL4、CXCL9和CXCL11的募集较少。CCL5与CXCL10的组合而非其他趋化因子显著增加了募集。将干扰素-γ、肿瘤坏死因子α和白细胞介素-1α共同注射以上调内皮细胞黏附分子表达，再与CXCL10或CCL5一起注射，可诱导淋巴母细胞迁移的累加性增加。因此，CXCR3配体在体外比CCR5配体更具趋化性；然而，在体内，CXCL10和CCL5对皮肤部位具有相当的T细胞募集活性，且比其他CXCR3和CCR5趋化因子更有效。所以，这些趋化因子诱导的体外趋化性不一定能预测其体内淋巴细胞募集活性。
