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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3718-3724.
Prepublished online as a Blood First Edition Paper on August 4, 2005; DOI 10.1182/blood-2005-04-1366.
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Submitted April 4, 2005
Accepted July 26, 2005
Human CD8+ T cells store CXCR1 in a distinct intracellular compartment and up-regulate it rapidly to the cell-surface upon activation
Olivier Gasser, Anna Missiou, Ceylan Eken, and Christoph Hess*
Department of Research, Immunobiology laboratory, University Hospital Basel, Basel, Switzerland
* Corresponding author; email: chess{at}uhbs.ch.
Activation and subsequent differentiation of naive CD8+ T cells leads to the development of memory-subsets with distinct homing and effector capacities. On non-lymphoid 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 upregulated to the cell-surface within minutes of activating human CD8+ T cells. No concurrent upregulation of other inflammatory chemokine receptors was observed. Upregulation of CXCR1 preferentially occurred on central memory CD8+ T cells - i.e. 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 or the lysosomal marker CD63. By contrast, partial colocalization with the Golgi marker GM130, the constitutive secretory pathway marker 2 microglobulin and the early endosome marker EEA1 was observed. Upregulation 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 upregulation. These results suggest that CD8+ T cells can rapidly adapt their homing properties by mobilizing CXCR1 from a distinct intracellular compartment.

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