Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer
Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer
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DOI：
10.1016/j.vetimm.2006.12.002
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发表时间：
2007-03-15
影响因子：
1.8
通讯作者：
Dow, S. W.
中科院分区：
文献类型：
--
作者：
Biller, B. J.;Elmslie, R. E.;Dow, S. W.
调节性T细胞（Treg）是一类独特的T淋巴细胞，具有免疫抑制特性，通常用于防止有害的自身免疫反应。然而，Tregs也可以干扰人类和啮齿动物的有益免疫反应，如抗肿瘤和抗病毒免疫。考虑到Tregs的总体重要性，它们很可能在狗的疾病中也起着重要作用。然而，目前还没有鉴定犬体内Tregs所需的试剂。因此，我们研究了FoxP3（一种在人类和啮齿动物中高度表达的转录因子）的表达是否也可以用于识别狗的Tregs。我们发现交叉反应性FoxP3抗体在狗的血液和淋巴结中识别出CD4(+)T细胞亚群。流式细胞术检测正常犬血液中FoxP3(+)CD4(+)T细胞的平均百分比为4.3%，淋巴结中FoxP3(+)CD4(+)T细胞的平均百分比为9.8%。在患有癌症的狗中，与年龄匹配的健康对照狗相比，血液中Treg的数量显著增加（7.5%），肿瘤引流淋巴结的数量显著增加（17.1%）。我们还发现，通过TCR激活并添加tgf - β和IL-2，狗的FoxP3(+)CD4(+)T细胞可以在体外显著扩增。处理后的细胞也显著增加tgf - β和IL-10 mRNA的表达。我们从这些研究中得出结论，交叉反应性FoxP3抗体可以用来鉴定狗的Treg，并且该试剂可以作为研究Treg在狗的各种疾病中的作用的有用工具。(c) 2007 Elsevier B.V.版权所有
Regulatory T cells (Treg) are a distinct group of T lymphocytes with immunosuppressive properties that serve normally to prevent harmful autoimmune responses. However, Tregs can also interfere with beneficial immune responses such as anti-tumor and anti-viral immunity in humans and rodents. Given the overall importance of Tregs, it is likely that they play an important role in diseases of dogs as well. However, at present reagents required for identification of Tregs in dogs are not available. Therefore, we investigated whether expression of FoxP3, a transcription factor that is highly expressed in Tregs in humans and rodents could also be used to identify Tregs in dogs. We found that a cross-reactive FoxP3 antibody identified a subset of CD4(+)T cells in blood and lymph nodes of dogs. By flow cytometry the mean percentage of FoxP3(+)CD4(+)T cells in normal dogs was 4.3% in blood and 9.8% in the lymph nodes. In dogs with cancer, there was a significant increase in numbers of Treg in blood (7.5%) and tumor-draining lymph nodes (17.1%) compared to age-matched healthy control dogs. We also found that FoxP3(+)CD4(+)T cells in dogs could be significantly expanded in vitro by TCR activation together with addition of TGF-beta and IL-2. Treated cells also significantly increased expression of TGF-beta and IL-10 mRNA. We conclude from these studies that a cross-reactive FoxP3 antibody can be used to identify Tregs in dogs and that this reagent may serve as a useful tool for investigating the role of Treg in a variety of diseases of dogs. (c) 2007 Elsevier B.V. All rights reserved.