Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice.
Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice.
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DOI：
10.1084/jem.20110466
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发表时间：
2011-11-21
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
--
作者：
Sela U;Olds P;Park A;Schlesinger SJ;Steinman RM
通过树突状细胞、转化生长因子 β 和视黄酸的同种刺激产生的调节性 T 细胞稳定表达 Foxp3，甚至可以抑制小鼠中正在进行的 GVHD。 Foxp3+调节性T细胞（T reg细胞）可有效抑制免疫，但尚不清楚抗原诱导的T reg细胞（iT reg细胞）是否能够在炎症条件下持续存在并稳定表达转录因子Foxp3。我们使用脾细胞在存在转化生长因子 β (TGF-β) 和视黄酸的情况下刺激混合白细胞反应 (MLR)。我们发现 CD11chigh 树突状细胞组分在诱导大量同种异体反应性 Foxp3+ 细胞方面最有效。诱导的CD4+CD25+Foxp3+细胞在广泛增殖后出现。当从 MLR 中纯化时，iT reg 细胞以抗原特异性方式在体外抑制初级和次级 MLR。转移至同种异体小鼠后，iT reg 细胞持续存在 6 个月，并预防由共转移 CD45RBhi T 细胞引起的移植物抗宿主病 (GVHD)。 GVHD 发生后转移 iT reg 细胞时也得到了类似的结果。持续存在的 iT reg 细胞中 Foxp3 基因的 CNS2 内含子序列与天然存在的 T reg 细胞的相应序列一样去甲基化。这些结果表明，诱导的 Foxp3+ T reg 细胞在增殖并分化为抗原特异性抑制性 T 细胞后，可以长期存在，同时抑制强大的炎症性疾病。
Regulatory T cells generated by allostimulation with dendritic cells, transforming growth factor β, and retinoic acid stably express Foxp3 and can suppress even ongoing GVHD in mice. Foxp3+ regulatory T cells (T reg cells) effectively suppress immunity, but it is not determined if antigen-induced T reg cells (iT reg cells) are able to persist under conditions of inflammation and to stably express the transcription factor Foxp3. We used spleen cells to stimulate the mixed leukocyte reaction (MLR) in the presence of transforming growth factor β (TGF-β) and retinoic acid. We found that the CD11chigh dendritic cell fraction was the most potent at inducing high numbers of alloreactive Foxp3+ cells. The induced CD4+CD25+Foxp3+ cells appeared after extensive proliferation. When purified from the MLR, iT reg cells suppressed both primary and secondary MLR in vitro in an antigen-specific manner. After transfer into allogeneic mice, iT reg cells persisted for 6 mo and prevented graft versus host disease (GVHD) caused by co-transferred CD45RBhi T cells. Similar findings were made when iT reg cells were transferred after onset of GVHD. The CNS2 intronic sequence of the Foxp3 gene in the persisting iT reg cells was as demethylated as the corresponding sequence of naturally occurring T reg cells. These results indicate that induced Foxp3+ T reg cells, after proliferating and differentiating into antigen-specific suppressive T cells, can persist for long periods while suppressing a powerful inflammatory disease.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
20.3
作者：
Blazar, BR;Taylor, PA;Vallera, DA
通讯作者：
Vallera, DA
影响因子：
20.3
作者：
Taylor, PA;Lees, CJ;Blazar, BR
通讯作者：
Blazar, BR
DOI：
10.1073/pnas.75.10.5132
发表时间：
1978-01-01
影响因子：
11.1
作者：
STEINMAN, RM;WITMER, MD
通讯作者：
WITMER, MD