CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intraturnoral CD4+CD25- T cells
CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intraturnoral CD4+CD25- T cells
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DOI：
10.1182/blood-2007-03-082578
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发表时间：
2007-10-01
期刊：
影响因子：
20.3
通讯作者：
Ansell, Stephen M.
中科院分区：
文献类型：
--
作者：
Yang, Zhi-Zhang;Novak, Anne J.;Ansell, Stephen M.
Foxp3的表达最初被认为仅限于CD4(+)CD25(+)调节性T细胞群。然而，最近的研究表明，Forkhead box P3(Foxp3)在老年小鼠的CD4(+)CD25(-)T细胞中表达。在目前对B细胞非霍奇金淋巴瘤(NHL)的研究中，我们发现，瘤内而不是外周血中的一部分CD4+CD25-T细胞表达Foxp3，能够抑制自体浸润性CD8(+)T细胞的增殖，约占瘤内CD4(+)T细胞的15%。体外用OKT3/抗CD28抗体(Ab)或树突状细胞(DC)激活后，这些CD4(+)CD25(-)Foxp3(-)T细胞亚群表达Foxp3。我们发现，在激活过程中，淋巴瘤B细胞的存在增强了激活诱导的CD4(+)CD25(-)T细胞中Foxp3的表达。我们还发现，CD70(+)淋巴瘤B细胞在激活诱导的肿瘤内CD4(+)CD25(-)T细胞中Foxp3的表达中起重要作用。此外，抗CD70单抗阻断CD27-CD70相互作用可阻断淋巴瘤B细胞介导的Foxp3在瘤内CD25(-)T细胞的表达。综上所述，这些研究揭示了非霍奇金淋巴瘤B细胞在肿瘤内调节性T细胞发展中的新作用。
Foxp3 expression was initially thought to be restricted to the CD4(+)CD25(+) regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4(+)CD25(-) T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25- T cells, comprising about 15% of intratumoral CD4(+) T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8(+) T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp3 expression in a subset of these CD4(+)CD25(-)Foxp3(-) T cells. We found that the presence of lymphoma B cells during activation augmented activation-induced Foxp3 expression in CD4(+)CD25(-) T cells. We also found that CD70(+) lymphoma B cells significantly contributed to the activation-induced Foxp3 expression in intratumoral CD4(+)CD25(-) T cells. Furthermore, the blockade of CD27-CD70 interaction by anti-CD70 Ab abrogated lymphoma B-cell-mediated induction of Foxp3 expression in intratumoral CD4(+)CD25(-) T cells. Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells.