Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
J Invest Dermatol. 2012 Jun;132(6):1636-44. doi: 10.1038/jid.2012.26. Epub 2012 Mar 1.
Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.
人类皮肤中的树突状细胞（DCs）分为表皮和真皮两个部分，它们在诱导 CD4+T 细胞和体液免疫应答方面表现出功能上的差异；然而，人类皮肤 DCs 对记忆性 CD8+T 细胞应答的调控差异仍未得到充分研究。我们测试了人类朗格汉斯细胞（LCs）和真皮树突状细胞（DDCs）诱导抗原特异性细胞因子产生和记忆性 CD8+细胞增殖的能力。尽管来自表皮和真皮两个部分的 TNF-α 成熟的人类 DCs 均具有有效激活 CD8+细胞的潜力，但 LCs 在交叉呈递 CD8+表位以及直接呈递 EBV 特异性 CD8+T 细胞方面的效率始终高于 DDCs。LCs 表达更高水平的 CD70，阻断 CD70-CD27 信号通路表明，表皮 LC 对 CD8+细胞的激活优势依赖于 CD70。LCs 通过 CD70 激活 CD8+细胞，这表明 LCs 在皮肤 CD8+免疫中发挥核心作用，并提示调控 LC CD70 的表达对于增强针对皮肤上皮病原体和癌症的免疫至关重要。
