A skin-selective homing mechanism for human immune surveillance T cells.
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-beta 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.
Schaerli
Patrick
P
Theodor-Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland.
Ebert
Lisa
L
Willimann
Katharina
K
Blaser
Andrea
A
Roos
Regula Stuber
RS
Loetscher
Pius
P
Moser
Bernhard
B
D015703:Antigens, CD / Q000097:blood / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015703:Antigens, CD; C103330:CCR8 protein, human; D016207:Cytokines; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing