Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells
Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells
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DOI：
10.1182/blood-2004-03-1211
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Roncarolo, MG
中科院分区：
文献类型：
--
作者：
Levings, MK;Gregori, S;Roncarolo, MG
树突状细胞（dc）是一种特殊的抗原呈递细胞，可以监测抗原环境并激活幼稚T细胞。dc的作用不仅是感知危险，而且在没有成熟/炎症刺激的情况下耐受免疫系统遇到的抗原。事实上，如果一个幼稚的T细胞在未成熟的dc （idc）上遇到它的抗原，它可能分化成T调节细胞（Tr）而不是T效应细胞。然而，人们对iDCs分化Tr细胞的机制知之甚少。我们开发了一种标准化和高度可重复的方案，通过将原始外周血CD4(+) T细胞反复暴露于异体干细胞来分化Tr细胞。由此产生的Tr细胞在表型和功能上与1型Tr （Tr1）细胞相同，因为它们的生成需要iDCs产生IL-10，并且它们通过白细胞介素-10 （IL-10）和转化生长因子- β (tgf - β)依赖机制抑制t细胞反应。此外，由idc诱导的TO细胞不需要CD4(+)CD25(+) Tr细胞的存在来生成，也不表达高组成水平的CD25或转录因子FoxP3。因此，iDCs可以驱动TO细胞的分化，并可用于产生大量异体抗原特异性TO细胞，用于临床，作为恢复外周耐受性的细胞疗法。(C) 2005年由美国血液病学会出版。
Dendritic cells (DCs) are specialized antigen-presenting cells that monitor the antigenic environment and activate naive T cells. The role of DCs is not only to sense danger but also to tolerize the immune system to antigens encountered in the absence of maturation/inflammatory stimuli. Indeed, if a naive T cell encounters its antigen on immature DCs (iDCs), it may differentiate into a T-regulatory (Tr) rather than a T-effector cell. However, little is known about the mechanisms by which iDCs differentiate Tr cells. We developed a standardized and highly reproducible protocol to differentiate Tr cells by repetitive exposure of naive peripheral blood CD4(+) T cells to allogeneic iDCs. The resultant Tr cells are phenotypically and functionally identical to type 1 Tr (Tr1) cells because their generation requires production of IL-10 by iDCs, and they suppress T-cell responses through an interleukin-10 (IL-10)- and a transforming growth factor beta (TGF-beta)-dependent mechanism. In addition, TO cells induced by iDCs do not require the presence of CD4(+)CD25(+) Tr cells for their generation, nor do they express high constitutive levels of CD25 or the transcription factor FoxP3. Thus, iDCs can drive the differentiation of TO cells and can be used to generate large numbers of alloantigen-specific TO cells for clinical use as a cellular therapy to restore peripheral tolerance. (C) 2005 by The American Society of Hematology.