IRF8-dependent DCs play a key role in the regulation of CD8 T cell responses to epithelial-derived antigen in the steady state but not in inflammation

Thorsten Joeris

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    Abstract

    Along the process of epithelial self-renewal, antigens derived from apoptotic intestinal epithelial cells (IECs) are taken up by antigen presenting cells (APCs), transported to gut-draining lymph nodes and crosspresented to CD8 T cells. In steady state, rapid tolerization of CD8 T cells reactive towards epithelialderived antigens is crucial to maintain tissue homeostasis. Since IRF8-dependent dendritic dells (IRF8-DCs) have superior cross-presenting capabilities, we aimed to investigate their role in this process. IFABP-tOva mice, expressing the model-antigen Ovalbumin (Ova) in IECs, were used as recipients to set up chimeras using either CD11c-cre.Irf8fl/fl bone marrow, which cannot generate IRF8-DCs, or cre-negative Irf8fl/fl control bone marrow. Whereas transfer of Ova-specific CD8 T cells (OT-I cells) to control chimeras resulted in their rapid tolerization, OT-I cells transferred to CD11c-cre.Irf8fl/fl chimeras spontaneously developed into cytotoxic effector T cells (CTL), causing epithelial destruction and intestinal inflammation. However, when the adjuvant R848 was applied in addition to OT-I transfer, inflammation was triggered in both, CD11ccre.Irf8fl/fl and control chimeras. This demonstrates that IRF8-DCs are crucial for the rapid tolerization of CD8 T cells reactive towards epithelial-derived antigen in steady state, but are not essential for the induction of CTLs in an inflammatory setting such as found in infection.
    Original languageEnglish
    Publication date2016
    Number of pages1
    Publication statusPublished - 2016
    Event10th European Mucosal Immunology Group meeting - Copenhagen, Denmark
    Duration: 19 Oct 201621 Oct 2016
    Conference number: 10

    Conference

    Conference10th European Mucosal Immunology Group meeting
    Number10
    CountryDenmark
    CityCopenhagen
    Period19/10/201621/10/2016

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