Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up-regulate it rapidly to the cell surface upon activation.
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 beta2-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.
Gasser
Olivier
O
Department of Research, Immunobiology Laboratory, University Hospital Basel, 20 Hebelstrasse, CH-4031 Basel, Switzerland.
Missiou
Anna
A
Eken
Ceylan
C
Hess
Christoph
C
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D021381:Protein Transport / Q000276:immunology*; D023062:Receptors, Interleukin-8A / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D023062:Receptors, Interleukin-8A