Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up-regulate it rapidly to the cell surface upon activation
Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up-regulate it rapidly to the cell surface upon activation
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DOI：
10.1182/blood-2005-04-1366
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发表时间：
2005-12-01
期刊：
影响因子：
20.3
通讯作者：
Hess, C
中科院分区：
文献类型：
--
作者：
Gasser, O;Missiou, A;Hess, C
初始CD8+T细胞的激活和随后的分化导致具有独特归巢和效应能力的记忆亚群的发育。在非淋巴归巢亚群中，“炎症”趋化因子受体（例如 CXCR3、CCR5、CX3CR1 和 CXCR1）的表达被认为可促进迁移至感染/炎症部位。在这里，我们证明CXCR1可以在激活人CD8(+) T细胞的几分钟内上调到细胞表面。没有观察到其他炎症趋化因子受体同时上调。 CXCR1 的上调优先发生在中央记忆 CD8+ T 细胞（即具有淋巴结归巢表型的细胞）上，并且具有功能相关性。免疫荧光显微镜显示CXCR1存在于细胞内囊泡中，其与穿孔素、RANTES（根据正常T细胞表达和分泌的激活而调节）或溶酶体标记物CD63没有显着共定位。相比之下，观察到与高尔基体标记 GM130、组成型分泌途径标记 β(2)-微球蛋白和早期内体标记 EEA1 的部分共定位。 T 细胞受体交联后，CXCR1 的上调并未发生。相比之下，来自活化的中性粒细胞的上清液，而不是来自单核细胞或树突状细胞的上清液，诱导其上调。这些结果表明CD8+T细胞可以通过从不同的细胞内区室动员CXCR1来快速适应其归巢特性。
Activation and subsequent differentiation of naive CD8(+) T cells lead to the development of memory subsets with distinct homing and effector capacities. On nonlymphoid homing subsets, expression of "inflammatory" chemokine receptors (such as CXCR3, CCR5, CX3CR1, and CXCR1) is believed to promote migration into sites of infection/ inflammation. Here we show that CXCR1 can be up-regulated to the cell surface within minutes of activating human CD8(+) T cells. No concurrent up-regulation of other inflammatory chemokine receptors was observed. Up-regulation of CXCR1 preferentially occurred on central memory CD8(+) T cells-that is, cells with a lymph node homing phenotype-and was functionally relevant. Immunofluorescence microscopy showed CXCR1 to be present in intracellular vesicles that do not significantly colocalize with perforin, RANTES (regulated upon activation normal T cell expressed and secreted), or the lysosomal marker CD63. By contrast, partial colocalization with the Golgi marker GM130, the constitutive secretory pathway marker beta(2)-microglobulin, and the early endosome marker EEA1 was observed. Up-regulation of CXCR1 did not occur after T-cell receptor cross-linking. By contrast, supernatants from activated neutrophils, but not from monocytes or dendritic cells, induced its up-regulation. These results suggest that CD8(+) T cells can rapidly adapt their homing properties by mobilizing CXCR1 from a distinct intracellular compartment.