Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo
Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8+ T cell crosspriming in vivo
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DOI：
10.1016/j.immuni.2006.01.005
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发表时间：
2006-02-01
期刊：
影响因子：
32.4
通讯作者：
Dubois, B
中科院分区：
文献类型：
--
作者：
Le Borgne, M;Etchart, N;Dubois, B
树突状细胞（DC[s]）在免疫后通过上皮组织有效地在体内启动CD8(+) CTL的性质在很大程度上仍然未知。在这里，我们发现髓系dc被佐剂迅速募集到颊粘膜或皮肤中，对于CD8(+) T细胞交叉游动是必不可少的。循环DC前体的募集，包括Gr1（+）单核细胞，通过CCR6/ ccl20依赖机制先于CD11c(+) MHC II类DC在真皮和上皮中的顺序积累。值得注意的是，CCR6的缺陷、CCL20的局部中和或单核细胞的消耗会阻止CD8(+) CTL在体内对佐剂给药的无害蛋白抗原的启动。此外，ccr6充足的Gr1（+）单核细胞的转移通过直接银呈递机制恢复CCRo/o小鼠的CD8(+) T细胞启动。因此，新募集的dc可能来源于循环单核细胞，在粘膜或皮肤免疫后，它们负责CD8(+) CTL的高效交叉增殖。
The nature of dendritic cell(s) (DC[s]) that conditions efficient in vivo priming of CD8(+) CTL after immunization via epithelial tissues remains largely unknown. Here, we show that myeloid DCs rapidly recruited by adjuvants into the buccal mucosa or skin are essential for CD8(+) T cell crosspriming. Recruitment of circulating DC precursors, including Gr1(+) monocytes, precedes the sequential accumulation of CD11c(+) MHC class II+ DCs in dermis and epithelium via a CCR6/CCL20-dependent mechanism. Remarkably, a defect in CCR6, local neutralization of CCL20, or depletion of monocytes prevents in vivo priming of CD8(+) CTL against an innocuous protein antigen administered with adjuvant. In addition, transfer of CCR6-sufficient Gr1(+) monocytes restores CD8(+) T cell priming in CCRo/o mice via a direct Ag presentation mechanism. Thus, newly recruited DCs likely derived from circulating monocytes are responsible for efficient crosspriming of CD8(+) CTL after mucosal or skin immunization.