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首页> 外文期刊>Journal of immunotherapy >Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross-presenting function.
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Maturation pathways of dendritic cells determine TAP1 and TAP2 levels and cross-presenting function.

机译：树突状细胞的成熟途径决定了TAP1和TAP2的水平以及交叉呈递功能。

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Ability to cross-present exogenous antigens in the human leukocyte antigen class I pathway is key to the antigen presenting function of mature tumor cell-loaded dendritic cells (DC). Conditions of DC maturation have been shown to be important for DCs ability to produce proinflammatory cytokines and induce T cell effector functions. However, it remains unknown if the different pathways of maturation are associated with modulation of the ability of mature DCs to cross-present tumor antigens (TA). Here, we compare DC matured with 3 clinically relevant cytokine combinations including interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6 (termed DC-0), DC-0 cells incubated with prostaglandin-2 (termed DC-0+prostaglandin-2), or DC treated with interferon-gamma, interferon-alpha, tumor necrosis factor-alpha, Poly I:C, and IL1-beta (termed DC-1). We found that these DC vary in their ability to cross-present TA to cytotoxic T lymphocytes (CTL), with the DC-1 cytokine combination being significantly more effective than the other 2. TA cross presentation and CTL priming were strongly correlated with level of expression of the antigen processing machinery components, TAP1 and TAP2, indicating that these components could be used as biomarkers to standardize DC preparations for optimal function. However, the up-regulation of TAP1/TAP2 was not sufficient to explain the enhanced cross-presentation ability of DC-1 cells, as the use of IFN-gamma alone to up-regulate TAP1/TAP2 did not generate DC as effective at cross-presentation as the full DC-1 maturation cytokine combination. These data indicate for the first time that the pathways of DC maturation modulate antigen processing machinery component expression to different extents and that differently matured DC vary in the ability to cross-present TA to human leukocyte antigen class I-restricted CTL.
机译：在人白细胞抗原I类途径中交叉呈递外源抗原的能力是成熟肿瘤细胞负载树突状细胞（DC）抗原呈递功能的关键。已经证明DC成熟的条件对于DC产生促炎细胞因子和诱导T细胞效应子功能的能力很重要。然而，尚不清楚不同的成熟途径是否与成熟DC交叉呈递肿瘤抗原（TA）的能力的调节有关。在这里，我们将DC与3种临床相关细胞因子组合（包括白介素（IL）-1 beta，肿瘤坏死因子-α，IL-6（称为DC-0），DC-0细胞与前列腺素2（称为DC- 0+前列腺素-2）或DC用干扰素-γ，干扰素-α，肿瘤坏死因子-α，Poly I：C和IL1-beta（称为DC-1）治疗。我们发现这些DC将TA交叉呈递给细胞毒性T淋巴细胞（CTL）的能力各不相同，而DC-1细胞因子组合的效果明显优于其他2种。TA交叉呈递和CTL引发与T细胞水平密切相关。抗原加工机械组件TAP1和TAP2的表达，表明这些组件可以用作生物标记物，以标准化DC制剂的最佳功能。但是，TAP1 / TAP2的上调不足以解释DC-1细胞的交叉表达能力增强，因为单独使用IFN-γ来上调TAP1 / TAP2的产生并不能有效地产生DC。 -表示为完整的DC-1成熟细胞因子组合。这些数据首次表明DC成熟的途径在不同程度上调节抗原加工机器组分的表达，并且不同成熟的DC在将TA交叉呈递给人白细胞抗原I类限制的CTL的能力方面有所不同。

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