Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
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DOI：
10.1084/jem.20030152
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发表时间：
2003-12-15
期刊：
影响因子：
--
通讯作者：
Wahl SM
中科院分区：
文献类型：
--
作者：
Chen W;Jin W;Hardegen N;Lei KJ;Li L;Marinos N;McGrady G;Wahl SM
CD 4 + CD 25+调节性T细胞（Treg）有助于维持免疫耐受。一个关键问题是Treg是否只能在胸腺中产生，或者可以从外周CD 4 + CD 25 −幼稚T细胞分化。在这篇论文中，我们提出了新的证据表明，幼稚外周CD 4 + CD 25 − T细胞转化为无反应性/抑制性细胞，即CD 25+，CD 45 RB −/低和细胞内CTLA-4+，可以通过与T细胞受体（TCR）和转化生长因子β（TGF-β）共刺激实现。虽然转录因子Foxp 3最近已被证明与Treg的发育有关，但Foxp 3基因表达的生理诱导剂仍然是一个谜。TGF-β诱导TCR激发的CD 4 + CD 25 −幼稚T细胞中Foxp 3基因表达，介导其向具有强效免疫抑制潜力的调节性T细胞表型转变。这些转化的无变应性/抑制性细胞不仅对TCR刺激无反应并且既不产生T辅助细胞1也不产生T辅助细胞2细胞因子，而且它们还表达TGF-β并在体外抑制正常T细胞增殖。更重要的是，在卵清蛋白肽TCR转基因过继转移模型中，TGF-β转化的转基因CD 4 + CD 25+抑制细胞响应于免疫而增殖，并在体内抑制抗原特异性幼稚CD 4 + T细胞扩增。最后，在小鼠哮喘模型中，共同给予这些TGF-β诱导的抑制性T细胞可预防室内尘螨诱导的肺过敏性发病机制。
CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or can differentiate from peripheral CD4+CD25− naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β). Although transcription factor Foxp3 has been shown recently to be associated with the development of Treg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-β induced Foxp3 gene expression in TCR-challenged CD4+CD25− naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-β and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-β–converted transgenic CD4+CD25+ suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4+ T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-β–induced suppressor T cells prevented house dust mite–induced allergic pathogenesis in lungs.
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影响因子：
32.4
作者：
Chen, WJ;Frank, ME;Wahl, SM
通讯作者：
Wahl, SM
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
DOI：
10.1084/jem.20020394
发表时间：
2002-07-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jonuleit H;Schmitt E;Kakirman H;Stassen M;Knop J;Enk AH
通讯作者：
Enk AH
DOI：
10.1084/jem.188.10.1849
发表时间：
1998-11-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen W;Jin W;Wahl SM
通讯作者：
Wahl SM
影响因子：
30.5
作者：
Apostolou, I;Sarukhan, A;von Boehmer, H
通讯作者：
von Boehmer, H