Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood.

Co-expression of TNFR2 and CD25 identifies more of the functional CD4+FOXP3+ regulatory T cells in human peripheral blood.
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DOI:
10.1002/eji.200940022
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发表时间:
2010-04
影响因子:
5.4
通讯作者:
Oppenheim, Joost J.
Oppenheim, Joost J.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Xin;Subleski, Jeffrey J.;Hamano, Ryoko;Howard, O. M. Zack;Wiltrout, Robert H.;Oppenheim, Joost J.

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之前我们发现 CD25 和 TNFR2 的共表达鉴定了小鼠调节性 T 细胞 (Treg) 中最具抑制性的子集。在这里,我们报告存在于 CD25high、CD25low 甚至 CD25− CD4 细胞亚群中的人外周血 (PB) FoxP3+ 细胞表达高水平的 TNFR2。因此,表达 TNFR2 的 CD4+CD25+ Tregs 包括 CD4+CD25high 子集中存在的所有 FoxP3+ 细胞以及 CD4+CD25low 子集中存在的相当大比例的 FoxP3+ 细胞。 CD4+CD25+TNFR2+细胞识别出的PB CD4淋巴细胞数量是CD4+CD25high细胞识别数量的5倍,并且表达的FoxP3+细胞水平与报道的CD4+CD25+CD127low/− Tregs相当。此外,该细胞群表现出特征性 Treg 表型,包括高水平 CTLA-4、CD45RO、CCR4 表达和低水平 CD45RA 和 CD127 表达。 TCR 刺激后,人 PB CD4+CD25+TNFR2+ 细胞呈无反应性,并显着抑制共培养 T 反应细胞的增殖和细胞因子产生。相反,CD4+CD25+TNFR2−和CD4+CD25−TNFR2+T细胞没有表现出抑制活性。由于一些非 Treg 表达 TNFR2,因此必须使用 CD25 和 TNFR2 的组合来识别更多的人类 Tregs 群体,这可能被证明对癌症和自身免疫性疾病的诊断和治疗有益。
Previously we found that co-expression of CD25 and TNFR2 identified the most suppressive subset of mouse regulatory T cells (Tregs). Here, we report that human peripheral blood (PB) FoxP3+ cells present in CD25high, CD25low and even CD25− subsets of CD4 cells expressed high levels of TNFR2. Consequently, TNFR2-expressing CD4+CD25+ Tregs included all of FoxP3+ cells present in CD4+CD25high subset as well as a substantial proportion of FoxP3+ cells present in CD4+CD25low subset. CD4+CD25+TNFR2+ cells identified 5-fold greater number of PB CD4 lymphocytes as Tregs than identified by CD4+CD25high cells, and expressed comparable levels of FoxP3+ cells as reported CD4+CD25+CD127low/− Tregs. Furthermore, this population of cells exhibited the characteristic Treg phenotype, including expression of high levels of CTLA-4, CD45RO, CCR4 and low levels of CD45RA and CD127. Upon TCR stimulation, human PB CD4+CD25+TNFR2+ cells were anergic and markedly inhibited the proliferation and cytokine production of co-cultured T responder cells. In contrast, CD4+CD25+TNFR2− and CD4+CD25− TNFR2+ T cells did not show inhibitory activity. Since some non-Tregs express TNFR2, the combination of CD25 and TNFR2 must be used to identify larger population of human Tregs, which may prove to be of diagnostic and therapeutic benefit in cancer and autoimmune diseases.
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发表时间: 2008-03-01
影响因子: 4.4
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