Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells.

Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells.
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DOI:
10.1084/jem.20021139
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发表时间:
2002-11-18
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Roncarolo MG
Roncarolo MG
中科院分区:
其他
文献类型:
--
作者:
Levings MK;Sangregorio R;Sartirana C;Moschin AL;Battaglia M;Orban PC;Roncarolo MG

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调节性T细胞(Tr细胞)对于诱导外周耐受至关重要。存在几种类型的Tr细胞,包括组成性表达CD25并通过直接的细胞间相互作用抑制免疫应答的CD4 + T细胞,以及通过分泌白细胞介素 - 10(IL - 10)和转化生长因子 - β(TGF - β)发挥作用的1型调节性T细胞(Tr1细胞)。CD25 + CD4 + T细胞和Tr1细胞之间的关系仍不清楚。在此,我们在克隆水平上证明Tr1细胞和CD25 + CD4 + T细胞是具有不同细胞因子产生谱的两种不同的调节性细胞亚群。此外,在没有CD25 + CD4 + T细胞的情况下,CD25 - CD4 + T细胞可被IL - 10诱导为无反应性并分化为Tr1细胞。克隆的人CD25 + CD4 + T细胞群是异质性的,只有一部分克隆持续高水平表达CD25且具有抑制性。CD25、细胞毒性T淋巴细胞抗原(CTLA) - 4和糖皮质激素诱导的肿瘤坏死因子(TNF)受体表达的强度与T细胞克隆的抑制能力相关。具有抑制功能的CD25 + CD4 + T细胞克隆均不产生IL - 10,但都产生TGF - β。由CD25 + CD4 + T细胞克隆介导的抑制作用部分依赖于TGF - β,但不依赖于CD25的组成性高表达。这些数据共同表明,天然存在的人CD25 + CD4 + T细胞不同于产生IL - 10的Tr1细胞。
T regulatory (Tr) cells are essential for the induction of peripheral tolerance. Several types of Tr cells exist, including CD4+ T cells which express CD25 constitutively and suppress immune responses via direct cell-to-cell interactions, and type 1 T regulatory (Tr1) cells, which function via secretion of interleukin (IL)-10 and transforming growth factor (TGF)-β. The relationship between CD25+CD4+ T cells and Tr1 cells remains unclear. Here, we demonstrate at the clonal level that Tr1 and CD25+CD4+ T cells are two distinct subsets of regulatory cells with different cytokine production profiles. Furthermore, CD25−CD4+ T cells can be rendered anergic by IL-10 and differentiated into Tr1 cells in the absence of CD25+CD4+ T cells. Cloned human CD25+CD4+ T cell populations are heterogeneous and only a subset of clones continues to express high levels of CD25 and is suppressive. The intensity of CD25, cytotoxic T lymphocyte antigen (CTLA)-4, and glucocorticoid-induced tumor necrosis factor (TNF) receptor expression correlates with the suppressive capacity of the T cell clones. None of the CD25+CD4+ T cell clones with suppressive function produce IL-10, but all produce TGF-β. Suppression mediated by CD25+CD4+ T cell clones is partially dependent on TGF-β, but not on constitutive high expression of CD25. Together these data indicate that naturally occurring human CD25+CD4+ T cells are distinct from IL-10–producing Tr1 cells.
DOI: 10.1084/jem.193.11.1303
发表时间: 2001-06-04
期刊: The Journal of experimental medicine
影响因子: --
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Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者: Schuler G
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