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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cross-presenting Human γδ T Cells Induce Robust Cd8~+ αβ T Cell Responses
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Cross-presenting Human γδ T Cells Induce Robust Cd8~+ αβ T Cell Responses

机译：交叉呈递的人γδT细胞诱导强大的Cd8〜+αβT细胞反应

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摘要

γδ T cells are implicated in host defense against microbes and tumors but their mode of function remains largely unresolved. Here, we have investigated the ability of activated human Vγ9Vδ2~+ T cells (termed γδ T-APCs) to cross-present microbial and tumor antigens to CD8~+ αβ T cells. Although this process is thought to be mediated best by DCs, adoptive transfer of ex vivo antigen-loaded, human DCs during immunotherapy of cancer patients has shown limited success. We report that γδ T-APCs take up and process soluble proteins and induce proliferation, target cell killing and cytokine production responses in antigen-experienced and naive CD8~+ αβ T cells. Induction of APC functions in Vγ9Vδ2~+ T cells was accompanied by the up-regulation of costimulatory and MHC class I molecules. In contrast, the functional predominance of the immunoproteasome was a characteristic of γδ T cells irrespective of their state of activation. γδ T-APCs were more efficient in antigen cross-presentation than monocyte-derived DCs, which is in contrast to the strong induction of CD4+ αβ T cell responses by both types of APCs. Our study reveals unexpected properties of human γδ T-APCs in the induction of CD8~+ αβ T effector cells, and justifies their further exploration in immunotherapy research.
机译：γδT细胞参与宿主对微生物和肿瘤的防御，但其功能模式在很大程度上尚未解决。在这里，我们研究了活化的人Vγ9Vδ2〜+ T细胞（称为γδT-APC）将微生物和肿瘤抗原交叉呈递给CD8〜+αβT细胞的能力。尽管认为该过程最好由DC介导，但是在癌症患者的免疫治疗过程中离体抗原加载的人DC的过继转移已显示出有限的成功。我们报道，γδT-APCs吸收并处理可溶性蛋白，并在经历过抗原和天然的CD8〜+αβT细胞中诱导增殖，靶细胞杀伤和细胞因子产生反应。在Vγ9Vδ2〜+ T细胞中APC功能的诱导伴随着共刺激分子和MHC I类分子的上调。相反，免疫蛋白酶体的功能优势是γδT细胞的特征，而与它们的活化状态无关。 γδT-APCs在抗原交叉呈递方面比单核细胞衍生的DCs更有效，这与两种类型的APC对CD4 +αβT细胞应答的强烈诱导相反。我们的研究揭示了人γδT-APCs在诱导CD8〜+αβT效应细胞中的出乎意料的特性，并为它们在免疫疗法研究中的进一步探索提供了依据。

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