Schaerli Patrick, Ebert Lisa, Willimann Katharina, Blaser Andrea, Roos Regula Stuber, Loetscher Pius, Moser Bernhard
Theodor-Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland.
J Exp Med. 2004 May 3;199(9):1265-75. doi: 10.1084/jem.20032177.
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.
有效的免疫监视对于维持外周组织的保护和内环境稳定至关重要。然而，控制记忆T细胞迁移至外周组织（如皮肤）的机制仍知之甚少。在此，我们发现健康皮肤中的大多数人类T细胞表达趋化因子受体CCR8，并对其选择性配体I-309/CCL1产生应答。这些CCR8(+) T细胞在小肠和结肠组织中不存在，在外周血中极为罕见，提示健康皮肤是它们的生理靶位点。皮肤CCR8(+) T细胞处于预激活状态，分泌促炎细胞因子，如肿瘤坏死因子-α和干扰素-γ，但缺乏细胞毒性T细胞的标志物。白细胞介素（IL）-4、IL-10和转化生长因子-β的分泌水平很低或无法检测到，这表明CCR8的表达与辅助性T细胞2或调节性T细胞亚群没有严格关联。外周血中皮肤监视T细胞的潜在前体可能对应于CCR8(+)CD25(-) T细胞的少数亚群。重要的是，CCL1在包括真皮微血管和表皮抗原呈递细胞在内的关键皮肤部位持续表达。这些发现首次定义了正常人皮肤中稳态T细胞运输的趋化因子系统。
