Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1(+) Dendritic Cells.

Optimal Generation of Tissue-Resident but Not Circulating Memory T Cells during Viral Infection Requires Crosspriming by DNGR-1(+) Dendritic Cells.
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DOI:
10.1016/j.immuni.2016.08.019
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发表时间:
2016-10-18
期刊:
影响因子:
32.4
通讯作者:
Sancho, David
Sancho, David
中科院分区:
医学1区
文献类型:
--
作者:
Iborra, Salvador;Martinez-Lopez, Maria;Khouili, Sofia C.;Enamorado, Michel;Cueto, Francisco J.;Conde-Garrosa, Ruth;del Fresno, Carlos;Sancho, David

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尽管组织驻留记忆T(Trm)细胞在保护性免疫中起着关键作用,但它们的启动机制仍然知之甚少。在这里,我们展示了Trm和循环记忆CD8+T细胞的不同启动要求。在痘苗病毒皮肤感染的小鼠中,DNGR-1介导的交叉压力是最佳Trm细胞启动所必需的,但不是为了它们的皮肤分化或循环记忆T细胞的产生。DNGR-1+树突状细胞(DC)促进T-bet转录因子的诱导和CD8+T细胞在淋巴结中的滞留。抑制LN出口可促进Trm细胞的生成,而DNGR-1的基因或抗体阻断DNGR-1或DNGR-1+DC在启动过程中提供的特定信号,如IL-12、IL-15或CD24,则会抑制Trm细胞的启动。DNGR-1还调节流感感染期间Trm细胞的生成。此外,保护性免疫依赖于DNGR-1+DC对Trm细胞的最佳诱导。我们的结果揭示了在病毒感染和疫苗接种过程中对CD8+Trm细胞的特殊启动要求。
Despite the crucial role of tissue-resident memory T (Trm) cells in protective immunity, their priming remains poorly understood. Here, we have shown differential priming requirements for Trm versus circulating memory CD8+ T cells. In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was required for optimal Trm cell priming but not for their skin differentiation or for circulating memory T cell generation. DNGR-1+ dendritic cells (DCs) promoted T-bet transcription factor induction and retention of CD8+ T cells in the lymph nodes (LNs). Inhibition of LN egress enhanced Trm cell generation, whereas genetic or antibody blockade of DNGR-1 or specific signals provided during priming by DNGR-1+ DCs, such as interleukin-12 (IL-12), IL-15 or CD24, impaired Trm cell priming. DNGR-1 also regulated Trm cell generation during influenza infection. Moreover, protective immunity depended on optimal Trm cell induction by DNGR-1+ DCs. Our results reveal specific priming requirements for CD8+ Trm cells during viral infection and vaccination.
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