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树突状细胞上的 CD5 调节 CD4+ 和 CD8+ T 细胞的激活和免疫应答的诱导。

CD5 on dendritic cells regulates CD4+ and CD8+ T cell activation and induction of immune responses.

机构信息

Department of Dermatology, University of Alabama at Birmingham. Birmingham, Alabama, United States of America.

Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.

出版信息

PLoS One. 2019 Sep 6;14(9):e0222301. doi: 10.1371/journal.pone.0222301. eCollection 2019.

DOI:10.1371/journal.pone.0222301
PMID:31491023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6730919/
Abstract

The role of CD5 as a regulator of T cell signaling and tolerance is well recognized. Recent data show expression of CD5 on different subtypes of human dendritic cells, however its functional relevance in modulating DC mediated responses remains poorly understood. In this study, we show CD5 is expressed on CD11c+ DC from murine thymus, lymph node, spleen, skin and lung. Although the development of DC subpopulations in CD5-/- mice was normal, CD5-deficient DC produced significantly higher levels of IL-12 than wild type DC in response to LPS. CD5-/- DC, in comparison to CD5+/+ DC, enhanced the activation of CD4+ and CD8+ T cells in vitro and in vivo and induced significantly higher production of IL-2 and IFN-gamma by T cells. Consequently, CD5-/- DC were significantly more potent than wild type DC in the induction of anti-tumor immunity and contact hypersensitivity responses in mice. Restoration of CD5 expression in CD5-/- DC reduced IL-12 production and inhibited their capacity to stimulate T cells. Collectively, these data demonstrate that the specific expression of CD5 on DC inhibits the production of inflammatory cytokines and has a regulatory effect on their activity to stimulate T cells and induce immune responses. This study reveals a previously unrecognized regulatory role for CD5 on DC and provides novel insights into mechanisms for DC biology in immune responses.

摘要

CD5 作为 T 细胞信号转导和耐受的调节剂的作用已得到广泛认可。最近的数据表明 CD5 在不同亚型的人类树突状细胞上表达，但其在调节 DC 介导的反应中的功能相关性仍知之甚少。在这项研究中，我们表明 CD5 表达于来自鼠胸腺、淋巴结、脾脏、皮肤和肺的 CD11c+ DC 上。尽管 CD5-/- 小鼠中 DC 亚群的发育正常，但与野生型 DC 相比，CD5 缺陷型 DC 在 LPS 刺激下产生的 IL-12 水平显著更高。与 CD5+/+ DC 相比，CD5-/- DC 在体外和体内增强了 CD4+和 CD8+ T 细胞的激活，并诱导 T 细胞产生显著更高水平的 IL-2 和 IFN-γ。因此，CD5-/- DC 在诱导小鼠抗肿瘤免疫和接触性超敏反应方面比野生型 DC 更有效。在 CD5-/- DC 中恢复 CD5 表达会降低 IL-12 的产生并抑制其刺激 T 细胞的能力。总之，这些数据表明 CD5 在 DC 上的特异性表达抑制了炎症细胞因子的产生，并对其刺激 T 细胞和诱导免疫反应的活性具有调节作用。这项研究揭示了 CD5 在 DC 上的一个以前未被认识的调节作用，并为 DC 生物学在免疫反应中的机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/86eed968418f/pone.0222301.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/b46885c9aade/pone.0222301.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/004fb8a02f13/pone.0222301.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/86eed968418f/pone.0222301.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/b9c618fe692c/pone.0222301.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/1fbc93288576/pone.0222301.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/34505c912069/pone.0222301.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f4/6730919/86eed968418f/pone.0222301.g007.jpg

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