Peyer's patch dendritic cells process viral antigen from apoptotic epithelial cells in the intestine of reovirus-infected mice
Peyer's patch dendritic cells process viral antigen from apoptotic epithelial cells in the intestine of reovirus-infected mice
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DOI：
10.1084/jem.20041132
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发表时间：
2004-07-19
影响因子：
15.3
通讯作者：
Kelsall, BL
中科院分区：
文献类型：
--
作者：
Fleeton, MN;Contractor, N;Kelsall, BL
我们探讨了Peyer‘s Patch(PP)树突状细胞(DC)群在诱导呼肠孤病毒1型Lang(T1L)株免疫应答中的作用。免疫荧光染色显示T1L感染小鼠的PPS中存在T1L结构蛋白(Sigma1)和非结构蛋白(SigmaNS)。滤泡相关上皮中的细胞同时含有sigma1和sigmaNS，这表明病毒的有效复制。相反，在与CD11c(+)/CD8α(-)/CD11b(Lo)树突状细胞相关的上皮下穹隆(SED)中检测到sigma1，而不是sigmaNS，提示这些DC在无感染的情况下摄取抗原。与这一可能性一致的是，从感染小鼠中纯化的PP DC含有sigma1，但不含sigmaNS，而从未感染小鼠的PP DC在体外不能产生感染。此外，末端脱氧UTP缺口末端标记显示SED中的Sigma1蛋白与DNA片段化、活化的caspase-3和上皮细胞蛋白细胞角蛋白相关，提示DC从感染的凋亡上皮细胞中捕获T1L抗原。最后，来自感染小鼠的PP树突状细胞在体外激活了T1L诱导的CD4(+)T细胞。这些研究表明，CD8α(-)/CD11b(Lo)树突状细胞。PP SED处理来自感染的凋亡上皮细胞的T1L抗原，将其呈递给CD4(+)T细胞，从而证明在自然病毒感染期间，体内DC交叉呈递病毒感染的细胞。
We explored the role of Peyer's patch (PP) dendritic cell (DC) populations in the induction of immune responses to reovirus strain type 1 Lang (T1L). Immunofluorescence staining revealed the presence of T1L structural (sigma1) and nonstructural (sigmaNS) proteins in PPs of T1L-infected mice. Cells in the follicle-associated epithelium contained both sigma1 and sigmaNS, indicating productive viral replication. In contrast, sigma1, but not sigmaNS, was detected in the subepithelial dome (SED) in association with CD11c(+)/CD8alpha(-)/CD11b(lo) DCs, suggesting antigen uptake by these DCs in the absence of infection. Consistent with this possibility, PP DCs purified from infected mice contained sigma1, but not sigmaNS, and PP DCs from uninfected mice could not be productively infected in vitro. Furthermore, sigma1 protein in the SED was associated with fragmented DNA by terminal deoxy-UTP nick-end labeling staining, activated caspase-3, and the epithelial cell protein cytokeratin, suggesting that DCs capture T1L antigen from infected apoptotic epithelial cells. Finally, PP DCs from infected mice activated T1L-primed CD4(+) T cells in vitro. These studies show that CD8alpha(-)/CD11b(lo) DCs in. the PP SED process T1L antigen from infected apoptotic epithelial cells for presentation to CD4(+) T cells, and therefore demonstrate the cross-presentation of virally infected cells by DCs in vivo during a natural viral infection.