Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.01887
Keywords
monocyte-derived dendritic cells; memory CD8(+) T cells; IFN-gamma; LCMV; acute infection
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Funding
- Basic Science Research Program [NRF-2018R1A2A1A05077627]
- Bio & Medical Technology Development Program through the National Research Foundation of Korea - Ministry of Science ICT [NRF-2016M3A9B5941426]
- National Research Foundation of Korea [2016M3A9B5941426] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Monocyte-derived dendritic cells (moDCs) have been shown to robustly expand during infection; however; their roles in anti-infectious immunity remain unclear. Here, we found that moDCs were dramatically increased in the secondary lymphoid organs during acute LCMV infection in an interferon-gamma (IFN-gamma)-dependent manner. We also found that priming by moDCs enhanced the differentiation of memory CD8(+) T cells compared to differentiation primed by conventional dendritic cells (cDCs) through upregulation of Eomesodermin (Eomes) and T cell factor-1 (TCF-1) expression in CD8(+) T cells. Consequently, impaired memory formation of CD8(+) T cells in mice that had reduced numbers of moDCs led to defective clearance of pathogens upon rechallenge. Mechanistically, attenuated interleukin-2 (IL-2) signaling in CD8(+) T cells primed by moDCs was responsible for the enhanced memory programming of CD8(+) T cells. Therefore, our findings unveil a specialization of the antigen-presenting cell subsets in the fate determination of CD8(+) T cells during infection and pave the way for the development of a novel therapeutic intervention on infection.
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