The Journal of Experimental Medicine
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Published 3 May 2004. doi:10.1084/jem.20032177
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1265-1275
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A Skin-selective Homing Mechanism for Human Immune Surveillance T Cells

Patrick Schaerli1, Lisa Ebert1, Katharina Willimann1, Andrea Blaser1, Regula Stuber Roos1, Pius Loetscher2, and Bernhard Moser1

1 Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
2 Novartis Institutes for Biomedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland

Address correspondence to Bernhard Moser, Theodor-Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland. Phone: 41-31-631-4157; Fax: 41-31-631-3799; email: bernhard.moser{at}tki.unibe.ch

Effective immune surveillance is essential for maintaining protection and homeostasis of peripheral tissues. However, mechanisms controlling memory T cell migration to peripheral tissues such as the skin are poorly understood. Here, we show that the majority of human T cells in healthy skin express the chemokine receptor CCR8 and respond to its selective ligand I-309/CCL1. These CCR8+ T cells are absent in small intestine and colon tissue, and are extremely rare in peripheral blood, suggesting healthy skin as their physiological target site. Cutaneous CCR8+ T cells are preactivated and secrete proinflammatory cytokines such as tumor necrosis factor–{alpha} and interferon-{gamma}, but lack markers of cytolytic T cells. Secretion of interleukin (IL)-4, IL-10, and transforming growth factor–ß was low to undetectable, arguing against a strict association of CCR8 expression with either T helper cell 2 or regulatory T cell subsets. Potential precursors of skin surveillance T cells in peripheral blood may correspond to the minor subset of CCR8+CD25– T cells. Importantly, CCL1 is constitutively expressed at strategic cutaneous locations, including dermal microvessels and epidermal antigen-presenting cells. For the first time, these findings define a chemokine system for homeostatic T cell traffic in normal human skin.

Key Words: chemokine • CCR8 • peripheral tissue • memory T cells • migration

The online version of this article contains supplemental material.

Abbreviations used in this paper: CLA, cutaneous lymphocyte-associated antigen; LC, Langerhans cell; TCM, central memory T cells; TEM, effector memory T cells; Treg, T regulatory.


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