Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential
Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential
复制标题
DOI：
10.1172/jci11902
复制
发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Butcher, EC
中科院分区：
文献类型：
--
作者：
Kim, CH;Kunkel, EJ;Butcher, EC
趋化因子受体的表达在t细胞发育过程中受到很好的控制。我们发现，新发现的趋化因子受体Bonzo/CXCR6在Th1或T细胞毒性1 （Tc 1）细胞亚群中表达，而在Th2或Tc2细胞中不表达，从而在体外和体内建立了Bonzo作为极化1型T细胞的差异标记物。树突状细胞诱导初始T细胞诱导Bonzo在T细胞上的表达。1L-12增强这种树突状细胞依赖性上调，而IL-4则抑制这种上调。在血液中，35-56%的Bonzo(+) CD4 T细胞为Th1细胞，60-65%的Bonzo(+) CD8 T细胞为Tc1细胞，少数Bonzo（+）细胞为2型T细胞。几乎所有的Bonzo(-) Tc1细胞都含有预先形成的颗粒酶A，并显示细胞毒性效应表型。大多数Bonzo(+) T细胞缺乏l -选择素和/或CCR7，这是淋巴组织的归巢受体。相反，Bonzo(+) T细胞在炎症组织部位的T细胞中显著富集，如类风湿关节和发炎的肝脏。Bonzo可能在介导1型炎症的效应T细胞的运输中起重要作用，使其成为炎症性疾病治疗调节的潜在靶点。
Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc 1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. 1L-12 enhances this dendritic cell-dependent upregulation, while IL-4 inhibits it. In blood, 35-56% of Bonzo(+) CD4 T cells are Th1 cells, and 60-65% of Bonzo(+) CD8 T cells are Tc1 cells, while few Bonzo(+) cells are type 2 T cells. Almost all Bonzo(-) Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo(+) T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo(+) T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases.