CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells.
CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells.
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DOI：
10.4049/jimmunol.181.10.6923
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
--
作者：
Yamazaki S;Dudziak D;Heidkamp GF;Fiorese C;Bonito AJ;Inaba K;Nussenzweig MC;Steinman RM
Foxp3+CD25+CD4+调节性T细胞介导免疫自身耐受，抑制免疫应答。肠道中树突状细胞（dc）的一个亚群专门以转化生长因子(TGF)-β和视黄酸（RA）依赖的方式诱导T - reg，从而实现口服耐受性。在这里，我们比较了小鼠脾脏的两个主要DC亚群。我们发现CD8+ DEC-205/CD205+ dc，而不是CD8 -树突状细胞抑制受体-2 (DCIR2)+ dc的主要部分，在低剂量抗原存在但不添加TGF-β的情况下，诱导Foxp3 -前体的功能性Foxp3+ T reg。CD8+ CD205+ dc优先表达TGF-β，这些dc在体外诱导T reg被TGF-β中和抗体阻断。相比之下，当外源性TGF-β供应时，CD8−DCIR2+ DCs能更好地诱导Foxp3+ T reg。在体内，CD8+ CD205+ dc同样优先诱导来自抗原特异性的DO11.10 RAG - / - Foxp3 - CD4+ T细胞的T reg，而CD8 - DCIR2+ dc更好地刺激天然Foxp3+ T reg。这些结果表明，脾脏（一个系统性淋巴器官）中的dc亚群专门分化外周Foxp3+ T regg，部分通过内源性TGF-β的形成。将抗原靶向这些dc可能有助于诱导抗原特异性Foxp3+ T reg，以治疗自身免疫性疾病、移植排斥和过敏。
Foxp3+CD25+CD4+ regulatory T cells (T reg) mediate immunological self-tolerance and suppress immune responses. A subset of dendritic cells (DCs) in the intestine is specialized to induce T reg in a transforming growth factor (TGF)-β and retinoic acid (RA) dependent manner to allow for oral tolerance. Here we compare two major DC subsets from mouse spleen. We find that CD8+ DEC-205/CD205+ DCs, but not the major fraction of CD8− dendritic cell inhibitory receptor-2 (DCIR2)+ DCs, induce functional Foxp3+ T reg from Foxp3− precursors in the presence of low doses of antigen but without added TGF-β. CD8+ CD205+ DCs preferentially express TGF-β, and the induction of T reg by these DCs in vitro is blocked by neutralizing antibody to TGF-β. In contrast, CD8− DCIR2+ DCs better induce Foxp3+ T reg when exogenous TGF-β is supplied. In vivo, CD8+ CD205+ DCs likewise preferentially induce T reg from adoptively transferred, antigen-specific, DO11.10 RAG−/− Foxp3− CD4+ T cells, whereas the CD8− DCIR2+ DCs better stimulate natural Foxp3+ T reg. These results indicate that a subset of DCs in spleen, a systemic lymphoid organ, is specialized to differentiate peripheral Foxp3+ T reg, in part through the endogenous formation of TGF-β. Targeting of antigen to these DCs might be useful for inducing antigen-specific Foxp3+ T reg for treatment of autoimmune diseases, transplant rejection and allergy.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
15.3
作者：
Apostolou, I;von Boehmer, H
通讯作者：
von Boehmer, H
影响因子：
15.3
作者：
Bayer, AL;Yu, AX;Adeegbe, D;Malek, TR
通讯作者：
Malek, TR
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
4.4
作者：
DiPaolo, Richard J.;Brinster, Carine;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.