T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies
T regulatory cells control T-cell proliferation partly by the release of soluble CD25 in patients with B-cell malignancies
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DOI：
10.1111/j.1365-2567.2010.03308.x
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发表时间：
2010-11-01
期刊：
影响因子：
6.4
通讯作者：
Loskog, Angelica S. I.
中科院分区：
文献类型：
--
作者：
Lindqvist, Camilla A.;Christiansson, Lisa H.;Loskog, Angelica S. I.
白细胞介素-2（IL-2）是研究最多的驱动T细胞增殖、活化和存活的细胞因子之一。它与IL-2受体结合，该受体由三条链组成，α链（CD 25）、β链和共同的γ链（γ c）。CD 25链与IL-2的结合是暴露β和γ c链的高亲和力结合位点所必需的，而β和γ c链又负责下游信号传导。高水平的可溶性CD 25（sCD 25）与非霍奇金淋巴瘤患者的不良预后相关。这种可溶性受体的功能和来源还没有得到很好的研究。在本研究中，我们假设调节性T细胞（Treg）可以释放CD 25作为IL-2的诱饵受体，从而剥夺T效应细胞的IL-2。通过多色流式细胞术和酶联免疫吸附试验研究了来自B细胞恶性肿瘤患者（n = 26）和健康对照（n = 27）的外周血中FoxP 3 + Treg细胞和sCD 25的存在和功能。此外，在存在或不存在重组sCD 25的情况下评价T细胞的增殖能力。结果表明，来自患者的Treg细胞具有较低的CD 25表达强度，并且它们在体外释放CD 25。此外，高水平的Treg细胞与sCD 25血浆浓度相关。重组sCD 25在体外可抑制T细胞增殖。总之，Treg细胞释放sCD 25可能是剥夺IL-2从而抑制抗肿瘤T细胞应答的机制。
P>Interleukin-2 (IL-2) is one of the most studied cytokines driving T-cell proliferation, activation and survival. It binds to the IL-2 receptor consisting of three chains, the alpha (CD25), beta and common gamma (gamma c). The binding of the CD25 chain to IL-2 is necessary to expose high-affinity binding sites for the beta and gamma c chains, which, in turn, are responsible for downstream signalling. A high level of soluble CD25 (sCD25) has been associated with a poor prognosis in patients with non-Hodgkin's lymphoma. The function and source of origin of this soluble receptor is not well investigated. In the present study we hypothesized that T regulatory (Treg) cells may release CD25 to act as a decoy receptor for IL-2, thereby depriving T-effector cells of IL-2. Peripheral blood from patients with B-cell malignancies (n = 26) and healthy controls (n = 27) was investigated for the presence and function of FoxP3+ Treg cells and sCD25 by multi-colour flow cytometry and enzyme-linked immunosorbent assay. Further, the proliferative capacity of T cells was evaluated with or without the presence of recombinant sCD25. The results demonstrate that Treg cells from patients had lower CD25 expression intensity and that they released CD25 in vitro. Further, high levels of Treg cells correlated with sCD25 plasma concentration. Recombinant sCD25 could suppress T-cell proliferation in vitro. In conclusion, the release of sCD25 by Treg cells may be a mechanism to deprive IL-2 and thereby inhibit anti-tumour T-cell responses.