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CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells

机译:CD127表达与FoxP3和人类CD4 + T reg细胞的抑制功能负相关

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摘要

Regulatory T (T reg) cells are critical regulators of immune tolerance. Most T reg cells are defined based on expression of CD4, CD25, and the transcription factor, FoxP3. However, these markers have proven problematic for uniquely defining this specialized T cell subset in humans. We found that the IL-7 receptor (CD127) is down-regulated on a subset of CD4+ T cells in peripheral blood. We demonstrate that the majority of these cells are FoxP3+, including those that express low levels or no CD25. A combination of CD4, CD25, and CD127 resulted in a highly purified population of T reg cells accounting for significantly more cells that previously identified based on other cell surface markers. These cells were highly suppressive in functional suppressor assays. In fact, cells separated based solely on CD4 and CD127 expression were anergic and, although representing at least three times the number of cells (including both CD25+CD4+ and CD25-CD4+ T cell subsets), were as suppressive as the "classic" CD4+CD25hi T reg cell subset. Finally, we show that CD127 can be used to quantitate T reg cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human T reg cells. JEM © The Rockefeller University Press.
机译:调节性T(T reg)细胞是免疫耐受的关键调节剂。大多数T reg细胞是根据CD4,CD25和转录因子FoxP3的表达定义的。然而,已证明这些标志物对于在人类中唯一定义该专门的T细胞亚群是有问题的。我们发现,IL-7受体(CD127)在外周血CD4 + T细胞的一个子集上被下调。我们证明这些细胞中的大多数是FoxP3 +,包括那些表达水平低或不表达CD25的细胞。 CD4,CD25和CD127的组合产生了高纯度的T reg细胞,占先前基于其他细胞表面标志物鉴定出的细胞数量明显增加。这些细胞在功能抑制试验中具有高度抑制性。实际上,仅基于CD4和CD127表达分离的细胞是无反应的,尽管其数量至少是细胞数量的三倍(包括CD25 + CD4 +和CD25-CD4 + T细胞亚群),但其抑制作用却与“经典” CD4一样+ CD25hi T reg细胞亚群。最后,我们证明CD127可用于定量1型糖尿病患者的T reg细胞亚群,支持CD127用作人类T reg细胞的生物标志物。 JEM©洛克菲勒大学出版社。

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