CCR7 expression and memory T cell diversity in humans
CCR7 expression and memory T cell diversity in humans
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DOI：
10.4049/jimmunol.166.2.877
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发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Wu, LJ
中科院分区：
文献类型：
--
作者：
Campbell, JJ;Murphy, KE;Wu, LJ
CCR7 与 L-选择素和 LFA-1 一起介导 T 细胞通过高位内皮小静脉 (HEV) 归巢至次级淋巴器官，CCR7 还涉及次级淋巴器官内淋巴细胞的微环境定位，以及淋巴细胞和树突状细胞在穿过非淋巴器官后返回淋巴液 组织。我们已经生成了针对人 CCR7 的单克隆抗体，其特异性与淋巴细胞亚群向已知 CCR7 配体的功能性迁移相关。我们发现 CCR7 在绝大多数外周血 T 细胞上表达，包括大多数表达归巢到非淋巴组织所需的粘附分子（皮肤淋巴细胞 Ag α (4)β (7) 整合素）的细胞。来自人外周血的 CD27(neg) 记忆 CD4 T 细胞亚群在 CCR7(neg) 群体以及 L-选择素(neg) 细胞中大量富集，表明这些细胞无法归巢至次级淋巴器官。因此，CD27阴性T细胞在扁桃体（代表性的次级淋巴器官）内很少见。次级淋巴器官内的所有静息 T 细胞都表达高水平的 CCR7，但许多活化细胞缺乏 CCR7，活化 CD4 细胞中 CCR7 的缺失伴随着 CXC 趋化因子受体 (CXCR)5 的增加，表明这两种受体的相互表达可能有助于器官内静息细胞与活化细胞的差异定位。从非淋巴组织（如皮肤、肺或肠）分离的淋巴细胞含有许多缺乏 CCR7 的 CD27(neg) 细胞。CD27(neg)/CCR7(neg) 细胞与 CD27(pos)/CCR7(pos) 细胞的比率因组织而异，并且可能与给定组织内积极参与 Ag 识别的细胞数量相关。
CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV), CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands, We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha (4)beta (7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7, CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7, The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.