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CD8+ T cell priming and provision of CD4+ T cell help are spatially and temporally distinct events

dc.contributor.advisorKastenmüller, Wolfgang
dc.contributor.authorEickhoff, Sarah
dc.description.abstractThe generation of a protective memory CD8+ T cell response requires priming of naïve T cells by dendritic cells and consecutive proliferation and differentiation of CD8+ T cells. In this differentiation process CD8+ T cells integrate multiple signals, including TCR-mediated stimulation, co-stimulation as well as cytokine-mediated activation. Co-stimulation and cytokine-mediated activation are in part dependent on CD4+ T cell helper signals. However, CD4+ T cell help for CD8+ T cells is not directly transmitted but rather provided by an intermediate cell population - dendritic cells.
In this study, I investigated which DC subset serves as the critical communication platform between CD4+ T helper and CD8+ T cells in order to optimize CD8+ T cell priming. Additionally, I aimed to address the spatio-temporal dynamics of such interactions in vivo, asking when and where those interactions may take place during an antiviral immune response. Interestingly, I found that CD4+ and CD8+ T cells were initially primed on spatial separated DC. CD8+ T cells were activated on directly infected DC in the periphery of the LN whereas CD4+ T cells were activated on non-infected DC in the LN paracortex. Notably, only during the later phase of infection (> 24h), both CD4+ and CD8+ T cells interacted with antigen-presenting non-infected XCR1+ DC within the paracortex of the LN. This critical activation step happened after the initial DC encounter of both lymphocyte subsets, but before they started to proliferate. On a functional level, I found that anti-viral CD8+ T cell responses activated in the absence of XCR1+ DC failed to differentiate into fully functional memory CD8+ T cells, mimicking the lack of CD4+ T cell help.
In conclusion, this study identifies a new phase of T cell programing that reveals multiple DC interactions during the initial lymphocyte priming step, is critical for the development of a functional memory CD8+ T cell compartment.
dc.rightsIn Copyright
dc.subject.ddc570 Biowissenschaften, Biologie
dc.titleCD8+ T cell priming and provision of CD4+ T cell help are spatially and temporally distinct events
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.instituteMedizinische Fakultät / Institute : Institut für Experimentelle Immunologie (IEI)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeKolanus, Waldemar

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