Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice

Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice
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DOI:
10.1016/j.intimp.2004.07.026
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发表时间:
2004-12-20
影响因子:
5.6
通讯作者:
Matsushima, K
Matsushima, K
中科院分区:
医学2区
文献类型:
--
作者:
Hontsu, S;Yoneyama, H;Matsushima, K

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CD 25 + CD 4+调节性T细胞(Treg)在宿主对肿瘤的应答中起关键作用。然而,它们在体内的确切位置在很大程度上是未知的。叉头/翼状螺旋转录因子Foxp 3在天然存在的Treg(nTreg)中特异性表达,并对其发育和功能进行编程。本研究制备了一种兔抗Foxp 3的多克隆抗体(pAb),该抗体能原位检测小鼠Foxp 3蛋白。使用该pAb的结果显示,Foxp 3 + CD 4 + nTreg细胞与正常和荷瘤小鼠淋巴组织的T细胞区域中的CD 11 c+树突状细胞(DC)以及Foxp 3-CD 4+和CD 8 +T淋巴细胞直接接触。Foxp 3 + CD 4 + nTreg细胞的数量在荷瘤小鼠的引流淋巴结(LN)和脾脏(SPL)中显著增加,但在非引流淋巴结(LN)和脾脏中不显著增加。此外,在肿瘤部位也可以发现少量的nTreg。这些观察结果支持肿瘤增加Foxp 3 + CD 4 + nTreg数量的观点,并可能导致在次级淋巴器官和肿瘤部位的荷瘤宿主中观察到的免疫抑制。(C)2004年由Elsevier B. V.出版
CD25+CD4+ regulatory T cells (Treg) play pivotal roles in the host response to tumors. However, their exact location in vivo is largely unknown. The forkhead/winged helix transcription factor, Foxp3, is specifically expressed in naturally occurring Treg (nTreg) and programs their development and function. In this study, we produced a rabbit polyclonal antibody (pAb), which can detect mouse Foxp3 protein in situ. Results using this pAb revealed that Foxp3+CD4+ nTreg cells occur in direct contact with CD11c+ dendritic cells (DCs), and Foxp3-CD4+ and CD8+T lymphocytes in the T cell regions of lymphoid tissues from normal and tumor-bearing mice. The numbers of Foxp3+CD4+ nTreg cells are significantly increased in draining, but not nondraining, lymph nodes (LNs) and spleen (SPL) of tumor-bearing mice. Furthermore, a small number of nTreg could be also found at the tumor site. These observations support the notion that the numbers of Foxp3+CD4+ nTreg are increased by tumors and may contribute to the immunosuppression observed in tumor-bearing hosts at secondary lymphoid organs and also possibly at the turnor site. (C) 2004 Published by Elsevier B.V.