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Type 1 Conventional CD103+ Dendritic Cells Control Effector CD8+ T Cell Migration, Survival, and Memory Responses During Influenza Infection

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  • Type 1 Conventional CD103+ Dendritic Cells Control Effector CD8+ T Cell Migration, Survival, and Memory Responses During Influenza Infection

    Front Immunol. 2018 Dec 21;9:3043. doi: 10.3389/fimmu.2018.03043. eCollection 2018.
    Type 1 Conventional CD103+ Dendritic Cells Control Effector CD8+ T Cell Migration, Survival, and Memory Responses During Influenza Infection.

    Ng SL1, Teo YJ1, Setiagani YA1, Karjalainen K1, Ruedl C1.
    Author information

    Abstract

    Type 1 conventional CD103+ dendritic cells (cDC1) contribute significantly to the cytotoxic T lymphocyte (CTL) response during influenza virus infection; however, the mechanisms by which cDC1s promote CTL recruitment and viral clearance are unclear. We demonstrate that cDC1 ablation leads to a deficient influenza-specific primary CD8+ T cell response alongside severe pulmonary inflammation, intensifying susceptibility to infection. The diminished pulmonary CTL population is not only a consequence of reduced priming in the lymph node (LN), but also of dysregulated CD8+ T cell egression from the LN and reduced CD8+ T cell viability in the lungs. cDC1s promote S1PR expression on CTLs, a key chemokine receptor facilitating CTL LN egress, and express high levels of the T cell survival cytokine, IL-15, to support CTL viability at the site of infection. Moreover, cDC1 ablation leads to severe impairment of CD8+ T cell memory recall and cross-reactive protection, suggesting that cDC1 are not only involved in primary T cell activation, but also in supporting the development of effective memory CD8+ T cell precursors. Our findings demonstrate a previously unappreciated and multifaceted role of CD103+ DCs in controlling pulmonary T cell-mediated immune responses.


    KEYWORDS:

    CD103; CD8+ T cell; Clec9A; dendritic cell; inflammation; influenza; migration; survival

    PMID: 30622538 PMCID: PMC6308161 DOI: 10.3389/fimmu.2018.03043
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