Rabin R L, Park M K, Liao F, Swofford R, Stephany D, Farber J M
Laboratory of Clinical Investigation, Flow Cytometry Unit, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
J Immunol. 1999 Apr 1;162(7):3840-50.
To address the issues of redundancy and specificity of chemokines and their receptors in lymphocyte biology, we investigated the expression of CC chemokine receptors CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 and responses to their ligands on memory and naive, CD4 and CD8 human T cells, both freshly isolated and after short term activation in vitro. Activation through CD3 for 3 days had the most dramatic effects on the expression of CXCR3, which was up-regulated and functional on all T cell populations including naive CD4 cells. In contrast, the effects of short term activation on expression of other chemokine receptors was modest, and expression of CCR2, CCR3, and CCR5 on CD4 cells was restricted to memory subsets. In general, patterns of chemotaxis in the resting cells and calcium responses in the activated cells corresponded to the patterns of receptor expression among T cell subsets. In contrast, the pattern of calcium signaling among subsets of freshly isolated cells did not show a simple correlation with receptor expression, so the propensity to produce a global rise in the intracellular calcium concentration differed among the various receptors within a given T cell subset and for an individual receptor depending on the cell where it was expressed. Our data suggest that individual chemokine receptors and their ligands function on T cells at different stages of T cell activation/differentiation, with CXCR3 of particular importance on newly activated cells, and demonstrate T cell subset-specific and activation state-specific responses to chemokines that are achieved by regulating receptor signaling as well as receptor expression.
为了解决趋化因子及其受体在淋巴细胞生物学中的冗余性和特异性问题，我们研究了CC趋化因子受体CCR1、CCR2、CCR3、CCR5、CXCR3和CXCR4在记忆性和初始性、CD4和CD8人T细胞上的表达情况，以及它们对配体的反应，这些细胞均为新鲜分离的细胞以及体外短期激活后的细胞。通过CD3激活3天对CXCR3的表达产生了最显著的影响，CXCR3在包括初始CD4细胞在内的所有T细胞群体中均上调且具有功能。相比之下，短期激活对其他趋化因子受体表达的影响较小，并且CD4细胞上CCR2、CCR3和CCR5的表达仅限于记忆亚群。一般来说，静息细胞中的趋化模式和激活细胞中的钙反应与T细胞亚群中的受体表达模式相对应。相比之下，新鲜分离细胞亚群中的钙信号模式与受体表达没有简单的相关性，因此在给定的T细胞亚群中，不同受体产生细胞内钙浓度整体升高的倾向不同，对于单个受体而言，这取决于其表达所在的细胞。我们的数据表明，单个趋化因子受体及其配体在T细胞激活/分化的不同阶段发挥作用，其中CXCR3在新激活的细胞上尤为重要，并证明了T细胞亚群特异性和激活状态特异性对趋化因子的反应，这些反应是通过调节受体信号传导以及受体表达来实现的。
