The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells

J. J. Campbell (), G. Haraldsen, J. Pan, J. Rottman, S. Qin, P. Ponath, D. P. Andrew (), R. Warnke, N. Ruffing, N. Kassam, L. Wu () and E. C. Butcher
Additional contact information
J. J. Campbell: Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine
G. Haraldsen: Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine
J. Pan: Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine
J. Rottman: LeukoSite Inc.
S. Qin: LeukoSite Inc.
P. Ponath: LeukoSite Inc.
D. P. Andrew: LeukoSite Inc.
R. Warnke: Stanford University School of Medicine
N. Ruffing: LeukoSite Inc.
N. Kassam: LeukoSite Inc.
L. Wu: LeukoSite Inc.
E. C. Butcher: Laboratory of Immunology and Vascular Biology, Stanford University School of Medicine

Nature, 1999, vol. 400, issue 6746, 776-780

Abstract: Abstract Lymphocytes that are responsible for regional (tissue-specific) immunity home from the blood to the intestines, inflamed skin or other sites through a multistep process involving recognition of vascular endothelial cells and extravasation1. Chemoattractant cytokine molecules known as chemokines2 regulate this lymphocyte traffic, in part by triggering arrest (stopping) of lymphocytes rolling on endothelium3,4,5. Here we show that many systemic memory T cells in blood carry the chemokine receptor CCR4 (ref. 6) and therefore respond to its ligands, the chemokines TARC and MDC. These cells include essentially all skin-homing cells expressing the cutaneous lymphocyte antigen and a subset of other systemic memory lymphocytes; however, intestinal (α4β7+) memory and naive T cells respond poorly. Immunohistochemistry reveals anti-TARC reactivity of venules and infiltration of many CCR4+ lymphocytes in chronically inflamed skin, but not in the gastrointestinal lamina propria. Moreover, TARC induces integrin-dependent adhesion of skin (but not intestinal) memory T cells to the cell-adhesion molecule ICAM-1, and causes their rapid arrest under physiological flow. Our results suggest that CCR4 and TARC are important in the recognition of skin vasculature by circulating T cells and in directing lymphocytes that are involved in systemic as opposed to intestinal immunity to their target tissues.

Date: 1999
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DOI: 10.1038/23495

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