CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells
CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells
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DOI：
10.1111/j.1365-2567.2006.02550.x
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发表时间：
2007-05-01
期刊：
影响因子：
6.4
通讯作者：
Gaston, J. S. Hill
中科院分区：
文献类型：
--
作者：
Duggleby, Richard C.;Shaw, Tovah N. F.;Gaston, J. S. Hill
很明显，调节性 T 细胞 (Treg) 在预防自身免疫和调节病原体反应方面发挥着重要作用。体外扩增 Treg 的实用方法将极大地促进人类患者 Treg 细胞功能的全面表征。扩增方法已有报道，但扩增后与新鲜分离的 Treg 相关的表面和细胞内标记物的表达是否与功能的维持相关尚不清楚。我们的目的是研究各种扩增方法并将调节活性与这些标记物的表达相关联。我们发现，在与新分离的 Treg 相关的标记中，只有 CD27 表达与调节活性相关，并且可用于从 CD4(+) CD25(+) 细胞扩增的细胞系中分离具有调节活性的细胞。此外，表达高水平转录因子叉头框 P3 (Foxp3) 的细胞仅限于这些细胞系内的 CD27(+) 群体。从CD4(+)CD25(-)细胞扩增的细胞系中，CD27的表达根据扩增所用的刺激而变化，但即使在测试CD27(+)细胞时，这些细胞系也不具有显着的调节活性。对反应性关节炎患者滑膜 CD4(+) CD25(+) 细胞的分析表明，它们主要是 CD27 阳性。这也适用于 CD25（高）和 CD25（中）CD4（+）细胞，尽管它们的调节能力不同。我们的结论是，虽然CD27可用于识别CD4（+）CD25（+）细胞扩增后获得的细胞系中的Treg细胞，但其表达可能无法可靠地识别其他T细胞群（例如关节中发现的T细胞）中的Treg细胞群。
It is clear that regulatory T cells (Treg) have an important role in preventing autoimmunity and modulating responses to pathogens. Full characterization of Treg cell function in human patients would be greatly facilitated by practical methods for expanding Treg in vitro. Methods for expansion have been reported but whether expression of surface and intracellular markers associated with freshly isolated Treg following expansion correlates with the maintenance of function is unclear. Our aim was to investigate the various methods of expansion and to correlate regulatory activity with expression of these markers. We show that, of the markers associated with freshly isolated Treg, only CD27 expression correlated with regulatory activity and could be used to isolate cells with regulatory activity from lines expanded from CD4(+) CD25(+) cells. Also, cells expressing high levels of the transcription factor forkhead box P3 (Foxp3) were confined to the CD27(+) population within these lines. Expression of CD27 by cells in lines expanded from CD4(+) CD25(-) cells varied depending on the stimulus used for expansion, but these lines did not have significant regulatory activity even when the CD27(+) cells were tested. Analysis of synovial CD4(+) CD25(+) cells from reactive arthritis patients revealed that they were predominantly CD27 positive. This also applied to CD25(high) and CD25(intermediate) CD4(+) cells, despite their reported different abilities to regulate. We conclude that, whilst CD27 is useful for identifying Treg in the cell lines obtained after expansion of CD4(+) CD25(+) cells, its expression may not reliably identify the Treg cell population in other T-cell populations such as those found in joints.