Langerin+CD8α+ Dendritic Cells Are Critical for Cross-Priming and IL-12 Production in Response to Systemic Antigens
Langerin+CD8α+ Dendritic Cells Are Critical for Cross-Priming and IL-12 Production in Response to Systemic Antigens
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DOI：
10.4049/jimmunol.0902707
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发表时间：
2009-12-15
影响因子：
4.4
通讯作者：
Hermans, Ian F.
中科院分区：
文献类型：
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作者：
Farrand, Kathryn J.;Dickgreber, Nina;Hermans, Ian F.
不同的树突状细胞（DC）亚群在银摄取途径和细胞内MHC I类或MHC 11类分子的路径方面存在差异。小鼠研究表明，CD8 α (+) DC在交叉呈递中具有特殊作用，其中外源性Ags在MHC I类分子上呈递给CD8(+) T细胞，而CD8 α (-) DC更有可能在MHC II类分子上呈递给CD4(+) T细胞。由于部分CD8 α (+) DC已被证明表达langerin(CD207)，我们研究了langerin(+)CD8 α (+) DC在呈递Ag和引发T细胞对可溶性Ag的反应中的作用。当从给药蛋白的动物中分选脾脏DC群体时，交叉呈递Ag的能力仅限于CD8 α (+) DC群体的langerin（+）区。langerin(+)CD8 α (+) DC群体在给予细胞色素c后也容易耗竭，已知细胞色素c如果转移到细胞质中会引发细胞凋亡。TLR2配体n -棕榈酰S-[2,3-双（棕榈酰氧基）-(2RS)-丙基]-[R]- cys -[S]- ser1 -[S]- lys4 -三盐酸或不变的NKT细胞配体α -半乳糖神经酰胺存在时，CTL的交叉启动在动物体内选择性地消耗langerin（+）细胞中严重受损。在这些系统激活刺激下，IL-12p40的产生仅限于朗格素（+）CD8 α (+) DC，在没有朗格素（+）细胞的情况下，不变的NKT细胞激活后，IL-12p70释放到血清中。这些数据表明CD8 α (+) DC群体的langerin（+）区在交叉启动和IL-12产生中起关键作用。中华免疫学杂志，2009,18(3):732- 742。
Distinct dendritic cell (DC) subsets differ with respect to pathways of Ag uptake and intracellular routing to MHC class I or MHC class 11 molecules. Murine studies suggest a specialized role for CD8 alpha(+) DC in cross-presentation, where exogenous Ags are presented on MHC class I molecules to CD8(+) T cells, while CD8 alpha(-) DC are more likely to present extracellular Ags on MHC class II molecules to CD4(+) T cells. As a proportion of CD8 alpha(+) DC have been shown to express langerin (CD207), we investigated the role of langerin(+)CD8 alpha(+) DC in presenting Ag and priming T cell responses to soluble Ags. When splenic DC populations were sorted from animals administered protein i.v., the ability to cross-present Ag was restricted to the langerin(+) compartment of the CD8 alpha(+) DC population. The langerin(+)CD8 alpha(+) DC population was also susceptible to depletion following administration of cytochrome c, which is known to trigger apoptosis if diverted to the cytosol. Cross-priming of CTL in the presence of the adjuvant activity of the TLR2 ligand N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-Cys-[S]-Ser1-[S]-Lys4-trihydrochloride or the invariant NKT cell ligand alpha-galactosylceramide was severely impaired in animals selectively depleted of langerin(+) cells in vivo. The production of IL-12p40 in response to these systemic activation stimuli was restricted to langerin(+)CD8 alpha(+) DC, and the release of IL-12p70 into the serum following invariant NKT cell activation was ablated in the absence of langerin(+) cells. These data suggest a critical role for the langerin(+) compartment of the CD8 alpha(+) DC population in cross-priming and IL-12 production. The Journal of Immunology, 2009, 183: 7732-7742.