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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Direct activation of antigen-presenting cells is required for CD8~+ T-cell priming and tumor vaccination
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Direct activation of antigen-presenting cells is required for CD8~+ T-cell priming and tumor vaccination

机译：CD8〜+ T细胞启动和肿瘤疫苗接种需要直接激活抗原呈递细胞

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摘要

Successful priming of adaptive immune responses is crucially dependent on innate activation signals that convert resting antigen-presenting cells (APCs) into immunogenic ones. APCs expressing the relevant innate pattern recognition receptors can be directly activated by pathogen-associated molecular patterns (PAMPs) to become competent to prime T-cell responses. Alternatively, it has been suggested that APCs could be activated indirectly by proin-flammatory mediators synthesized by PAMP-exposed cells. However, data obtained with CD4+ T cells suggest that inflammatory signals often cannot substitute for direct pattern recognition in APC activation for the priming of T helper responses. To test whether the same is true for CD8+ T cells, we studied cytotoxic T lymphocyte development in vitro and in mixed chimeric mice in which coexisting APCs can either present a preprocessed model antigen or directly recognize a given PAMP, but not both. We show that indirectly activated APCs promote antigen-specific proliferation of naive CD8+ T cells but fail to support their survival and cytotoxic T lymphocyte differentiation. Furthermore, CD8* T cells primed by indirectly activated APCs are unable to reject tumors. Thus, inflammation cannot substitute for direct recognition of single PAMPs in CD8+ T-cell priming. These findings have important practical implications for vaccine design, indicating that adjuvants must be judiciously chosen to trigger the relevant pattern recognition receptors in APCs.
机译：适应性免疫应答的成功启动关键取决于先天激活信号，该信号将静止的抗原呈递细胞（APC）转换成免疫原性。表达相关的先天性模式识别受体的APC可以被病原体相关的分子模式（PAMP）直接激活，从而具有引发T细胞反应的能力。备选地，已经提出APC可以被暴露于PAMP的细胞合成的前炎性炎性介质间接激活。但是，用CD4 + T细胞获得的数据表明，炎症信号通常不能代替APC激活中直接模式识别来引发T辅助反应。为了测试CD8 + T细胞是否同样如此，我们研究了体外和混合嵌合小鼠的细胞毒性T淋巴细胞发育，其中共存的APC可以呈递预处理的模型抗原或直接识别给定的PAMP，但不能同时识别两者。我们显示间接激活的APC促进幼稚CD8 + T细胞的抗原特异性增殖，但不能支持其生存和细胞毒性T淋巴细胞分化。此外，间接激活的APC引发的CD8 * T细胞无法排斥肿瘤。因此，炎症不能替代CD8 + T细胞引发中单个PAMP的直接识别。这些发现对疫苗设计具有重要的实际意义，表明必须谨慎选择佐剂以触发APC中的相关模式识别受体。

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    Wolfgang Kratky; Caetano Reis e Sousa; Annette Oxenius; Roman Sporri;

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    Institute for Microbiology, Eidgenossische Technische Hochschule Zurich, 8093 Zurich, Switzerland;

    lmmunobiology Laboratory, Cancer Research UK,London Research Institute, London WC2A 3LY, United Kingdom;

    Institute for Microbiology, Eidgenossische Technische Hochschule Zurich, 8093 Zurich, Switzerland;

    Institute for Microbiology, Eidgenossische Technische Hochschule Zurich, 8093 Zurich, Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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