Regulatory T-cell function of adult T-cell leukemia/lymphoma cells
Regulatory T-cell function of adult T-cell leukemia/lymphoma cells
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DOI：
10.1002/ijc.22536
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发表时间：
2007-05-01
影响因子：
6.4
通讯作者：
Ueda, Ryuzo
中科院分区：
文献类型：
--
作者：
Yano, Hiroki;Ishida, Takashi;Ueda, Ryuzo
成人T细胞白血病/淋巴瘤(ATLL)患者免疫功能高度低下，但导致这种状态的潜在机制仍不清楚。最近的研究表明，FOXP3是自然产生的调节性T(Treg)细胞的主控基因，在ATLL的一部分患者的肿瘤细胞中表达。由于大多数ATLL细胞同时表达CD4和CD25，根据其表型特征，这些肿瘤可能起源于CD4(+)CD25(+)FOXP3(+)Treg细胞。然而，ATLL细胞是否真的发挥Treg细胞的功能还没有得到明确的证明。在这里，我们证明了来自患者亚群的ATLL细胞不仅对T细胞受体介导的激活反应迟钝，而且还抑制了自体CD4(+)非ATLL细胞的增殖。此外，来自这一亚群患者的ATLL细胞只分泌少量的干扰素-γ，并抑制自体CD4(+)非ATLL细胞产生的干扰素-γ。这些数据首次表明，来自患者子集的ATLL细胞在自体设置中作为Treg细胞发挥功能。这项研究为理解ATLL的免疫发病机制，即HTLV-1感染的细胞如何面对宿主免疫反应而存活提供了新的见解。这也增加了我们对ATLL患者免疫功能严重受损状态的了解。(C)2007年Wiley-Liss，Inc.
Adult T-cell leukemia/lymphoma (ATLL) patients are highly immunocompromised, but the underlying mechanism responsible for this state remains obscure. Recent studies demonstrated that FOXP3, which is a master control gene of naturally occurring regulatory T (Treg) cells, is expressed in the tumor cells from a subset of patients with ATLL. Since most ATLL cells express both CD4 and CD25, these tumors might originate from CD4(+)CD25(+)FOXP3(+) Treg cells, based on their phenotypic characteristics. However, whether ATLL cells actually function as Treg cells has not yet been clearly demonstrated. Here, we show that ATLL cells from a subset of patients are not only hypo-responsive to T-cell receptor-mediated activation, but also suppress the proliferation of autologous CD4(+) non-ATLL cells. Furthermore, ATLL cells from this subset of patients secrete only small amounts of IFN-gamma, and suppress IFN-gamma production by autologous CD4(+) non-ATLL cells. These are the first data showing that ATLL cells from a subset of patients function as Treg cells in an autologous setting. The present study provides novel insights into understanding the immunopathogenesis of ATLL, i.e., how HTLV-1-infected cells can survive in the face of host immune responses. It also adds to our understanding of ATLL patients' severely immunocompromised state. (c) 2007 Wiley-Liss, Inc.