CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells

CD169+ macrophages are sufficient for priming of CTLs with specificities left out by cross-priming dendritic cells
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DOI:
10.1073/pnas.1423356112
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发表时间:
2015-04-28
影响因子:
11.1
通讯作者:
Brocker, Thomas
Brocker, Thomas
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bernhard, Caroline A.;Ried, Christine;Brocker, Thomas

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树突状细胞 (DC) 被认为是最有效的抗原呈递细胞 (APC),可直接引发或交叉引发 MHC I 限制性细胞毒性 T 细胞 (CTL)。然而,最近的证据表明存在其他尚未鉴定的 APC 也能够启动 T 细胞。为了识别这些 APC,我们使用了腺病毒 (rAd) 载体,该载体不感染 DC,但选择性地在 CD169(+) 巨噬细胞 (MP) 中积累。在缺乏 DC 的小鼠中,CD169(+) MP 的感染足以引发对所有测试表位具有特异性的 CTL。相反,完全依赖于交叉呈递 DC 的 CTL 反应仅偏向于选定的强 MHC I 结合肽。当 DC 和 MP 都缺席时,无法引发 CTL 反应。因此,CD169(+) MP可以被认为是对CTL反应有显着贡献的APC。
Dendritic cells (DCs) are considered the most potent antigen-presenting cells (APCs), which directly prime or cross-prime MHC I-restricted cytotoxic T cells (CTLs). However, recent evidence suggests the existence of other, as-yet unidentified APCs also able to prime T cells. To identify those APCs, we used adenoviral (rAd) vectors, which do not infect DCs but selectively accumulate in CD169(+) macrophages (MPs). In mice that lack DCs, infection of CD169(+) MPs was sufficient to prime CTLs specific for all epitopes tested. In contrast, CTL responses relying exclusively on cross-presenting DCs were biased to selected strong MHC I-binding peptides only. When both DCs and MPs were absent, no CTL responses could be elicited. Therefore, CD169(+) MPs can be considered APCs that significantly contribute to CTL responses.