Rabin Ronald L, Alston Marc A, Sircus Janna C, Knollmann-Ritschel Barbara, Moratz Chantal, Ngo Diana, Farber Joshua M
Laboratories of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2003 Sep 15;171(6):2812-24. doi: 10.4049/jimmunol.171.6.2812.
Chemokine receptors on T cells are frequently categorized as functioning either in immune system homeostasis within lymphoid organs, or in peripheral inflammation. CXCR3 is in the latter category and is reported to be expressed selectively on Th1 cells. We found that CXCR3 was expressed in vivo on newly activated tonsillar CD4(+) T cells. Using CD4(+) T cells from cord blood, we found that CXCR3 was induced by cellular activation in vitro independently of the cytokine milieu, although on resting cells, expression was maintained preferentially on those that had been activated in type 1 conditions. In inflamed tonsils, CXCR3(+)CD4(+) T cells were localized around and within germinal centers. The inference that CXCR3 has a role in germinal center reactions was supported by the finding that the CXCR3 ligand CXC chemokine ligand 9 was expressed in a pattern demarcating a subset of germinal centers both in tonsil and in lymph nodes from an HIV-infected individual. We next investigated the role of CXCR3 on peripheral effector/memory CD4(+) T cells by comparing its pattern of expression with that of CCR5, another Th1-cell associated chemokine receptor. Analysis of cells directly from peripheral blood and after activation in vitro suggested that CXCR3 expression preceded that of CCR5, supporting a model of sequential induction of chemokine receptors during CD4(+) T cell differentiation. Taken together, our data show that CXCR3 can be expressed at all stages of CD4(+) T cell activation and differentiation, bridging central function in lymphoid organs and effector function in peripheral tissues.
T细胞上的趋化因子受体通常被归类为在淋巴器官内的免疫系统稳态中发挥作用，或在周围炎症中发挥作用。CXCR3属于后者，据报道它在Th1细胞上选择性表达。我们发现CXCR3在体内新激活的扁桃体CD4(+) T细胞上表达。利用脐血中的CD4(+) T细胞，我们发现CXCR3在体外可由细胞激活诱导产生，且与细胞因子环境无关，不过在静息细胞上，CXCR3优先在1型条件下被激活的细胞上维持表达。在发炎的扁桃体中，CXCR3(+)CD4(+) T细胞定位于生发中心周围和内部。CXCR3配体CXC趋化因子配体9在HIV感染个体的扁桃体和淋巴结中以一种划分生发中心子集的模式表达，这一发现支持了CXCR3在生发中心反应中起作用的推断。接下来，我们通过比较CXCR3与另一种Th1细胞相关趋化因子受体CCR5的表达模式，研究了CXCR3在外周效应/记忆CD4(+) T细胞上的作用。对直接来自外周血的细胞以及体外激活后的细胞进行分析表明，CXCR3的表达先于CCR5，这支持了CD4(+) T细胞分化过程中趋化因子受体顺序诱导的模型。综上所述，我们的数据表明CXCR3可在CD4(+) T细胞激活和分化的所有阶段表达，在淋巴器官的中枢功能和外周组织的效应功能之间架起桥梁。
