Trogocytosis of CD80 and CD86 by induced regulatory T cells
Trogocytosis of CD80 and CD86 by induced regulatory T cells
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DOI：
10.1038/cmi.2011.62
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发表时间：
2012-03-01
影响因子：
24.1
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Gu, Peng;Gao, Julia Fang;Zhang, Li
胞吞作用是一个涉及膜碎片和细胞表面蛋白在细胞之间转移的过程。各种类型的T细胞已被证明能够从抗原呈递细胞获得膜结合蛋白，并且它们的功能可以在胞啃作用后被调节。然而，目前尚不清楚诱导的调节性T细胞（iT细胞）是否可以进行胞刺，如果是这样的话，这个过程的功能后果可能需要什么。在这项研究中，我们表明，iTclase可以从CD 80（-/-）CD 86（-/-）双敲除（DKO）小鼠中产生。使用流式细胞术和共聚焦荧光显微镜，我们证明了从DKO小鼠产生的iTcells能够从成熟树突状细胞（mDC）获得CD 80和CD 86，并且CD 86的获得比CD 80的获得程度更高。此外，我们发现与iTdR共孵育后，树突状细胞（DC）下调其表面CD 80和CD 86的表达。CD 80和CD 86的胞吞作用以细胞毒性T淋巴细胞相关抗原-4（CTLA-4）、CD 28和程序性死亡配体-1（PDL 1）非依赖性方式发生。重要的是，我们发现，与未获得CD 86的iTclone相比，从mDC获得CD 86的iTclone表达更高的活化标志物，并且它们抑制幼稚CD 4（+）T细胞增殖的能力增强。这些数据首次证明，iTclad可以从mDC获得CD 80和CD 86，并且CD 86的获得可以增强它们的抑制功能。这些发现为iTreg和DC之间的相互作用提供了新的理解，表明胞啃作用可能在iTreg介导的免疫抑制中起重要作用。Cellular & Molecular Immunology（2012）9，136-146; doi：10.1038/cmi.2011.62;在线发表2012年2月6日
Trogocytosis is a process which involves the transfer of membrane fragments and cell surface proteins between cells. Various types of T cells have been shown to be able to acquire membrane-bound proteins from antigen-presenting cells and their functions can be modulated following trogocytosis. However, it is not known whether induced regulatory T cells (iTregs) can undergo trogocytosis, and if so, what the functional consequences of this process might entail. In this study, we show that iTregs can be generated from CD80(-/-)CD86(-/-) double knockout (DKO) mice. Using flow cytometry and confocal fluorescence microscopy, we demonstrate that iTregs generated from DKO mice are able to acquire both CD80 and CD86 from mature dendritic cells (mDCs) and that the acquisition of CD86 occurs to a higher extent than that of CD80. Furthermore, we found that after co-incubation with iTregs, dendritic cells (DCs) downregulate their surface expression of CD80 and CD86. The trogocytosis of both CD80 and CD86 occurs in a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), CD28 and programmed death ligand-1 (PDL1)-independent manner. Importantly, we showed that iTregs that acquired CD86 from mDCs expressed higher activation markers and their ability to suppress naive CD4(+) T-cell proliferation was enhanced, compared to iTregs that did not acquire CD86. These data demonstrate, for the first time, that iTregs can acquire CD80 and CD86 from mDCs, and the acquisition of CD86 may enhance their suppressive function. These findings provide novel understanding of the interaction between iTregs and DCs, suggesting that trogocytosis may play a significant role in iTreg-mediated immune suppression. Cellular & Molecular Immunology (2012) 9, 136-146; doi: 10.1038/cmi.2011.62; published online 6 February 2012