A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.
A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity.
复制标题
DOI：
10.1016/j.immuni.2011.03.029
复制
发表时间：
2011-07-22
期刊：
影响因子：
32.4
通讯作者：
Williams CB
中科院分区：
文献类型：
--
作者：
Haribhai D;Williams JB;Jia S;Nickerson D;Schmitt EG;Edwards B;Ziegelbauer J;Yassai M;Li SH;Relland LM;Wise PM;Chen A;Zheng YQ;Simpson PM;Gorski J;Salzman NH;Hessner MJ;Chatila TA;Williams CB
虽然天然和诱导的调节性T（nTreg和iTreg）细胞都可以增强耐受性，但它们协同作用的机制尚未建立。我们通过新生Foxp3缺陷小鼠的过继转移免疫治疗来检查nTreg和iTreg细胞的功能。作为单一疗法，只有nTreg细胞可以预防疾病致死，但不能抑制慢性炎症和自身免疫。用nTreg细胞提供足够Foxp3的常规T细胞重建了iTreg库并建立了耐受性。反过来，在获救的小鼠中iTreg细胞的急性消耗导致体重减轻和炎症。尽管nTreg和体内衍生的iTreg细胞的转录特征紧密匹配，但它们的T细胞受体（TCR）库中存在最小的重叠。因此，iTreg细胞是补充nTreg细胞的必需的非冗余调节亚群，部分地通过扩大调节应答内的TCR多样性。
Although both natural and induced regulatory T (nTreg and iTreg) cells can enforce tolerance, the mechanisms underlying their synergistic actions have not been established. We examined the functions of nTreg and iTreg cells by adoptive transfer immunotherapy of newborn Foxp3-deficient mice. As monotherapy, only nTreg cells prevented disease lethality, but did not suppress chronic inflammation and autoimmunity. Provision of Foxp3-sufficient conventional T cells with nTreg cells reconstituted the iTreg pool and established tolerance. In turn, acute depletion of iTreg cells in rescued mice resulted in weight loss and inflammation. Whereas the transcriptional signatures of nTreg and in vivo derived iTreg cells were closely matched, there was minimal overlap in their T cell receptor (TCR) repertoires. Thus, iTreg cells are an essential non-redundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within regulatory responses.
登录
查看更多内容
影响因子：
32.4
作者：
Fontenot, JD;Rasmussen, JP;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
通讯作者：
Rudensky, AY
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
5.4
作者：
Huter, Eva N.;Punkosdy, George A.;Glass, Deborah D.;Cheng, Lily I.;Ward, Jerrold M.;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.