Plasmacytoid dendritic cells mediate oral tolerance.

Plasmacytoid dendritic cells mediate oral tolerance.
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DOI:
10.1016/j.immuni.2008.06.017
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发表时间:
2008-09-19
期刊:
影响因子:
32.4
通讯作者:
Kaiserlian, Dominique
Kaiserlian, Dominique
中科院分区:
医学1区
文献类型:
--
作者:
Goubier, Anne;Dubois, Bertrand;Gheit, Hanane;Joubert, Grgoire;Villard-Truc, Florence;Asselin-Paturel, Carine;Trinchieri, Giorgio;Kaiserlian, Dominique

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口服耐受可防止口服对饮食抗原(Ags)(包括蛋白质和半抗原)的致敏作用,以及迟发型超敏反应(DTH)的发生。我们发现浆细胞样树突状细胞(pDC)阻止口服T细胞引发,并负责对由Ag喂养诱导的CD4+和CD8+ T细胞介导的DTH反应的全身耐受。pDC的系统性消耗防止了通过抗原喂养诱导耐受。将口服载银的肝脏pDC转移至幼稚受体小鼠,分别诱导了对蛋白质和半抗原的CD4+和CD8+ T细胞应答的Ag特异性抑制。肝脏是口服Ag呈递的部位,并且pDC似乎通过CD4+ T细胞非依赖性机制相对快速地诱导肝脏中Ag特异性T细胞的无反应性或缺失。这些数据表明,口服耐受依赖于pDC向T细胞的Ag呈递,并表明pDC可以代表肠道和全身性炎性疾病的关键治疗靶标。
Oral tolerance prevents oral sensitization to dietary antigens (Ags), including proteins and haptens, and development of delayed-type hypersensitivity (DTH) responses. We showed here that plasmacytoid dendritic cells (pDCs) prevented oral T cell priming and were responsible for systemic tolerance to CD4+ and CD8+ T cell-mediated DTH responses induced by Ag feeding. Systemic depletion of pDCs prevented induction of tolerance by antigen feeding. Transfer of oral Ag-loaded liver pDCs to naive recipient mice induced Ag-specific suppression of CD4+ and CD8+ T cell responses to protein and hapten, respectively. Liver is a site of oral Ag presentation, and pDCs appeared to induce anergy or deletion of Ag-specific T cells in the liver relatively rapidly via a CD4+ T cell-independent mechanism. These data demonstrate that oral tolerance relies on Ag presentation by pDC to T cells and suggest that pDC could represent a key therapeutic target for intestinal and systemic inflammatory diseases.
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