Eickhoff, Sarah: CD8+ T cell priming and provision of CD4+ T cell help are spatially and temporally distinct events. - Bonn, 2018. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5n-51269
@phdthesis{handle:20.500.11811/7593,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5n-51269,
author = {{Sarah Eickhoff}},
title = {CD8+ T cell priming and provision of CD4+ T cell help are spatially and temporally distinct events},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2018,
month = jul,

note = {The 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.},

url = {http://hdl.handle.net/20.500.11811/7593}
}

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