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A Skin-selective Homing Mechanism for Human Immune Surveillance T Cells

2004; Rockefeller University Press; Volume: 199; Issue: 9 Linguagem: Inglês

10.1084/jem.20032177

1540-9538

Patrick Schaerli, Lisa M. Ebert, Katharina Willimann, Andrea Blaser, Regula Stuber Roos, Pius Loetscher, Bernhard Moser,

Immunotherapy and Immune Responses

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–α and interferon-γ, but lack markers of cytolytic T cells. Secretion of interleukin (IL)-4, IL-10, and transforming growth factor–β 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.