The differential production of cytokines by human Langerhans cells and dermal CD14+ DCs controls CTL priming
The differential production of cytokines by human Langerhans cells and dermal CD14+ DCs controls CTL priming
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DOI：
10.1182/blood-2011-08-371245
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发表时间：
2012-06-14
期刊：
影响因子：
20.3
通讯作者：
Klechevsky, Eynav
中科院分区：
文献类型：
--
作者：
Banchereau, Jacques;Thompson-Snipes, Luann;Klechevsky, Eynav
我们最近报道，人表皮朗格汉斯细胞(LCS)比真皮CD14(+)树突状细胞(DC)更有效地将初始CD8(+)T细胞激发成强大的CTL。我们推测，独特的树突状细胞(DC)细胞因子表达谱(即LCS产生的IL-15和真皮CD14(+)DC表达的IL-10)可能解释了观察到的功能差异。在CD8(+)T细胞启动过程中阻断IL-15可使T细胞的增殖减少约50%。这些被IL-15剥夺的CD8(+)T细胞没有获得效应记忆细胞的表型。它们分泌较少的IL-2和干扰素-γ，仅表达少量的CD107a、颗粒酶和穿孔素，并降低了抗凋亡蛋白Bcl-2的水平。共聚焦显微镜分析表明，IL-15定位于LCS和初始CD8(+)T细胞的免疫突触。相反，在真皮CD14(+)DC和初始CD8(+)T细胞共培养过程中阻断IL-10可促进效应CTL的产生，而在LCS和初始CD8(+)T细胞培养中加入IL-10则抑制其诱导。由真皮CD14(+)DC转录的转化生长因子-β1进一步增强了IL-10的抑制作用。因此，IL-15和IL-10的产生解释了LCS和真皮CD14(+)树突状细胞对CD8(+)T细胞启动的不同作用。(血。2012年；119(24)：5742-5749)
We recently reported that human epidermal Langerhans cells (LCs) are more efficient than dermal CD14(+) DCs at priming naive CD8(+) T cells into potent CTLs. We hypothesized that distinctive dendritic cell (DC) cytokine expression profiles (ie, IL-15 produced by LCs and IL-10 expressed by dermal CD14(+) DCs) might explain the observed functional difference. Blocking IL-15 during CD8(+) T-cell priming reduced T-cell proliferation by similar to 50%. These IL-15-deprived CD8(+) T cells did not acquire the phenotype of effector memory cells. They secreted less IL-2 and IFN-gamma and expressed only low amounts of CD107a, granzymes and perforin, and reduced levels of the antiapoptotic protein Bcl-2. Confocal microscopy analysis showed that IL-15 is localized at the immunologic synapse of LCs and naive CD8(+) T cells. Conversely, blocking IL-10 during cocultures of dermal CD14(+) DCs and naive CD8(+) T cells enhanced the generation of effector CTLs, whereas addition of IL-10 to cultures of LCs and naive CD8(+) T cells inhibited their induction. TGF-beta 1 that is transcribed by dermal CD14(+) DCs further enhanced the inhibitory effect of IL-10. Thus, the respective production of IL-15 and IL-10 explains the contrasting effects of LCs and dermal CD14(+) DCs on CD8(+) T-cell priming. (Blood. 2012; 119(24):5742-5749)