Malignant B cells induce the conversion of CD4+CD25- T cells to regulatory T cells in B-cell non-Hodgkin lymphoma.
Malignant B cells induce the conversion of CD4+CD25- T cells to regulatory T cells in B-cell non-Hodgkin lymphoma.
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DOI：
10.1371/journal.pone.0028649
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Han Y;Wu J;Bi L;Xiong S;Gao S;Yin L;Jiang L;Chen C;Yu K;Zhang S
最近的证据表明，调节性T细胞（Treg）在b细胞非霍奇金淋巴瘤（NHL）患者的肿瘤部位富集。然而，富集的原因和抑制机制需要进一步阐明。我们发现，与健康志愿者（HVs）相比，新诊断的b细胞NHL患者CD4+CD25+FoxP3+CD127lo Treg在外周血（PB）和骨髓（BM）中明显增加，且其表型不同。受累淋巴组织也比良性淋巴结显示更高的Treg频率。此外，在同一患者中，受累淋巴组织中Treg的频率明显高于PB和BM。与同种异体cfse标记的CD4+CD25 -应答细胞共培养的CD4+CD25 - Treg介导的抑制在b细胞NHL的受灶淋巴组织中也高于由hv的Treg介导的抑制。此外，我们发现恶性B细胞在体外显著诱导CD4+CD25−T细胞中FoxP3的表达和调控功能。相比之下，正常B细胞不能诱导CD4+CD25−T细胞转化为Treg。我们还发现PD-1/B7-H1通路可能在Treg诱导中发挥重要作用。综上所述，我们的研究结果表明，恶性B细胞诱导CD4+CD25−T细胞转化为Treg，这可能在B细胞NHL的发病机制中发挥作用，并代表了一个有希望的治疗靶点。
Recent evidence has demonstrated that regulatory T cells (Treg) were enriched in the tumor sites of patients with B-cell non-Hodgkin lymphoma (NHL). However, the causes of enrichment and suppressive mechanisms need to be further elucidated. Here we demonstrated that CD4+CD25+FoxP3+CD127lo Treg were markedly increased and their phenotypes were different in peripheral blood (PB) as well as bone marrow (BM) from newly diagnosed patients with B-cell NHL compared with those from healthy volunteers (HVs). Involved lymphatic tissues also showed higher frequencies of Treg than benign lymph nodes. Moreover, the frequencies of Treg were significantly higher in involved lymphatic tissues than those from PB as well as BM in the same patients. Suppression mediated by CD4+CD25+ Treg co-cultured with allogeneic CFSE-labeled CD4+CD25− responder cells was also higher in involved lymphatic tissues from B-cell NHL than that mediated by Treg from HVs. In addition, we found that malignant B cells significantly induced FoxP3 expression and regulatory function in CD4+CD25− T cells in vitro. In contrast, normal B cells could not induce the conversion of CD4+CD25− T cells to Treg. We also showed that the PD-1/B7-H1 pathway might play an important role in Treg induction. Taken together, our results suggest that malignant B cells induce the conversion of CD4+CD25− T cells to Treg, which may play a role in the pathogenesis of B-cell NHL and represent a promising therapeutic target.
影响因子：
3.7
作者：
Yu Y;Miller J;Leventhal JR;Tambur AR;Chandrasekaran D;Levitsky J;Luo X;Mathew JM
通讯作者：
Mathew JM