Human liver dendritic cells promote T cell hyporesponsiveness.
Human liver dendritic cells promote T cell hyporesponsiveness.
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DOI：
10.4049/jimmunol.0803404
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发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
DeMatteo RP
中科院分区：
文献类型：
--
作者：
Bamboat ZM;Stableford JA;Plitas G;Burt BM;Nguyen HM;Welles AP;Gonen M;Young JW;DeMatteo RP
肝脏被认为促进耐受性，这可能是有益的，因为它不断暴露于来自门静脉循环的外来Ag。虽然树突状细胞（DC）是免疫应答的关键介质，但对人类肝脏DC知之甚少。我们比较了新鲜纯化的肝DCs从手术标本与自体血DCs。肝脏和血液DC同样不成熟，但有不同的子集组成。BDCA-1+ DC代表最普遍的肝DC亚群，而大多数外周血DC是CD 16+。TLR 4连接后，血液DC分泌多种促炎细胞因子，而肝脏DC产生大量IL-10。在原代MLR和再刺激后，肝脏DC诱导同种异体T细胞增殖较少。同样，Ag特异性CD 4 + T细胞在最初由自体肝DC而不是血液DC刺激时对再刺激的反应较低。此外，肝DC通过IL-10依赖性机制产生更多的抑制性CD 4 + CD 25 + FoxP 3 + T调节细胞和IL-4产生性Th 2细胞。我们的发现对于理解肝脏免疫至关重要，并证明人类肝脏DC促进免疫低反应性，可能有助于肝脏耐受。
The liver is believed to promote tolerance, which may be beneficial due to its constant exposure to foreign Ags from the portal circulation. Although dendritic cells (DCs) are critical mediators of immune responses, little is known about human liver DCs. We compared freshly purified liver DCs from surgical specimens with autologous blood DCs. Liver and blood DCs were equally immature, but had distinct subset compositions. BDCA-1+ DCs represented the most prevalent liver DC subset, whereas the majority of peripheral blood DCs were CD16+. Upon TLR4 ligation, blood DCs secreted multiple proinflammatory cytokines, whereas liver DCs produced substantial amounts of IL-10. Liver DCs induced less proliferation of allogeneic T cells both in a primary MLR and after restimulation. Similarly, Ag-specific CD4+ T cells were less responsive to restimulation when initially stimulated by autologous liver DCs rather than blood DCs. In addition, liver DCs generated more suppressive CD4+ CD25+FoxP3+ T regulatory cells and IL-4-producing Th2 cells via an IL-10-dependent mechanism. Our findings are critical to understanding hepatic immunity and demonstrate that human liver DCs promote immunologic hyporesponsiveness that may contribute to hepatic tolerance.
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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
DOI：
10.1084/jem.190.2.229
发表时间：
1999-07-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iwasaki A;Kelsall BL
通讯作者：
Kelsall BL
影响因子：
13.5
作者：
Nattermann, Jacob;Zimmermann, Henning;Spengler, Ulrich
通讯作者：
Spengler, Ulrich
影响因子：
20.3
作者：
MacDonald, KPA;Munster, DJ;Hart, DNJ
通讯作者：
Hart, DNJ
影响因子：
4.4
作者：
Dzionek, A;Fuchs, A;Schmitz, J
通讯作者：
Schmitz, J