Cross-presenting human γδ T cells induce robust CD8+ αβ T cell responses
Cross-presenting human γδ T cells induce robust CD8+ αβ T cell responses
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DOI：
10.1073/pnas.0810059106
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发表时间：
2009-02-17
影响因子：
11.1
通讯作者：
Moser, Bernhard
中科院分区：
文献类型：
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作者：
Brandes, Marlene;Willimann, Katharina;Moser, Bernhard
γ δ T细胞参与宿主对微生物和肿瘤的防御，但它们的功能模式在很大程度上仍未得到解决。在这里，我们研究了活化的人V γ 9V δ 2（+）T细胞（称为γ δ T-APC）交叉呈递微生物和肿瘤抗原至CD 8（+）α β T细胞的能力。尽管该过程被认为最好由DC介导，但在癌症患者的免疫治疗期间，离体抗原负载的人DC的过继转移已显示出有限的成功。我们报道了γ δ T-APCs摄取和加工可溶性蛋白质，并诱导抗原经历的和幼稚的CD 8（+）α β T细胞的增殖、靶细胞杀伤和细胞因子产生应答。在V γ 9V δ 2（+）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γ δ T细胞的特征，而不管它们的活化状态如何。γ δ T-APC在抗原交叉呈递中比单核细胞衍生的DC更有效，这与两种类型的APC对CD 4（+）α β T细胞应答的强烈诱导形成对比。我们的研究揭示了人γ δ T-APCs在诱导CD 8（+）α β T效应细胞中的意想不到的特性，并证明了它们在免疫治疗研究中的进一步探索。
gamma delta 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 V gamma 9V delta 2(+) T cells ( termed gamma delta T-APCs) to cross-present microbial and tumor antigens to CD8(+) alpha beta 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 gamma delta T-APCs take up and process soluble proteins and induce proliferation, target cell killing and cytokine production responses in antigen-experienced and naive CD8(+) alpha beta T cells. Induction of APC functions in V gamma 9V delta 2(+) 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 gamma delta T cells irrespective of their state of activation. gamma delta T-APCs were more efficient in antigen cross-presentation than monocyte-derived DCs, which is in contrast to the strong induction of CD4(+) alpha beta T cell responses by both types of APCs. Our study reveals unexpected properties of human gamma delta T-APCs in the induction of CD8(+) alpha beta T effector cells, and justifies their further exploration in immunotherapy research.