IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation
IFN-γ enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation
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DOI：
10.1073/pnas.0405947101
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发表时间：
2004-10-05
影响因子：
11.1
通讯作者：
Gnjatic, S
中科院分区：
文献类型：
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作者：
Matsuo, M;Nagata, Y;Gnjatic, S
我们比较了单核细胞来源的树突状细胞和转化生长因子β 1诱导的朗格汉斯样细胞（LC）交叉呈递外源性NY-ESO-1蛋白/抗体免疫复合物至NY-ESO-1特异性CD 8（+）T细胞克隆的能力。与树突状细胞相反，LC不能组成性地将NY-ESO-1交叉呈递给T细胞克隆，但在用IFN-γ处理后可以。值得注意的是，这种IFN-γ诱导的特征既不是由于增强的抗原摄取，也不是由于促进LC中的抗原加工。相反，IFN-γ至少部分地通过增强其他难治性LC的成熟而起作用，从而使外源性抗原能够到达加工机器。该条件交叉呈递模型建立了IFN-γ作为有效免疫调节剂的原始作用水平，并支持IFN-γ在靶向LC的蛋白质疫苗接种策略中的使用。
We compared monocyte-derived dendritic cells and transforming growth factor-beta1-induced Langerhans-like cells (LCs) for their capacity to cross-present exogenous NY-ESO-1 protein/antibody immune complexes to an NY-ESO-1-specific CD8(+) T cell clone. In contrast to dendritic cells, LCs were not able to cross-present NY-ESO-1 to the T cell clone constitutively but did so after treatment with IFN-gamma. Remarkably, this IFN-gamma-inducible characteristic was due neither to enhanced antigen uptake nor to facilitated antigen processing in LCs. Rather, IFN-gamma acted at least in part by potentiating the maturation of otherwise refractory LCs, enabling in turn exogenous antigen to reach the processing machinery. This model of conditional cross-presentation establishes an original level of action for IFN-gamma as an effective immune modulator and supports the use of IFN-gamma in protein vaccination strategies targeting LCs.