Agace W W, Roberts A I, Wu L, Greineder C, Ebert E C, Parker C M
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Eur J Immunol. 2000 Mar;30(3):819-26. doi: 10.1002/1521-4141(200003)30:3<819::AID-IMMU819>3.0.CO;2-Y.
To determine which chemokine receptors might be involved in T lymphocyte localization to the intestinal mucosa, we examined receptor expression on human intestinal lamina propria lymphocytes (LPL), intraepithelial lymphocytes (IEL) and CD45RO+beta7hi gut homing peripheral blood lymphocytes (PBL). Virtually all LPL and IEL expressed CXCR3 and CCR5, receptors that have been associated with Th1(Tc1)/Th0 lymphocytes, while CCR3 and CCR4, receptors associated with Th2 (Tc2)lymphocytes, CCR7, CXCR1 and CXCR2 were not expressed. CXCR3 and CCR5 receptors were functional, as LPL and IEL migrated to their respective ligands I-TAC and RANTES. In addition, most alphaEbeta7- LPL and IEL expressed high levels of CCR2. While the majority of CD45RO(-)beta7hi PBL also expressed CXCR3 and CCR5, a proportion of these cells were CXCR3- and/or CCR5- and some expressed CCR4 and/or CCR7, indicating that lymphocytes recruited to the intestinal mucosa represent a subset of these cells. In summary, our results show that LPL and IEL within the normal intestine express a specific and similar array of chemokine receptors whose ligands are constitutively expressed in the intestinal mucosa and whose expression is up-regulated during intestinal inflammation. These results support the view that CXCR3, CCR5 and CCR2 may play an important role in lymphocyte localization within the intestinal mucosa.
为了确定哪些趋化因子受体可能参与T淋巴细胞在肠道黏膜的定位，我们检测了人肠道固有层淋巴细胞（LPL）、上皮内淋巴细胞（IEL）以及CD45RO+β7hi肠道归巢外周血淋巴细胞（PBL）上的受体表达情况。几乎所有的LPL和IEL都表达CXCR3和CCR5，这两种受体与Th1（Tc1）/Th0淋巴细胞相关，而与Th2（Tc2）淋巴细胞相关的CCR3和CCR4、CCR7、CXCR1和CXCR2则未表达。CXCR3和CCR5受体具有功能，因为LPL和IEL会迁移至它们各自的配体I-TAC和RANTES。此外，大多数αEβ7-LPL和IEL都高水平表达CCR2。虽然大多数CD45RO（-）β7hi PBL也表达CXCR3和CCR5，但这些细胞中有一部分是CXCR3-和/或CCR5-，还有一些表达CCR4和/或CCR7，这表明募集到肠道黏膜的淋巴细胞只是这些细胞中的一个亚群。总之，我们的结果显示，正常肠道内的LPL和IEL表达一组特定且相似的趋化因子受体，其配体在肠道黏膜中组成性表达，且在肠道炎症期间表达上调。这些结果支持以下观点：CXCR3, CCR 和CCR2可能在淋巴细胞在肠道黏膜内的定位中发挥重要作用。
