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Verfasst von:Frank, Roland [VerfasserIn]   i
 Gabel, Michael [VerfasserIn]   i
 Heiß, Kirsten [VerfasserIn]   i
 Müller, Ann-Kristin [VerfasserIn]   i
 Graw, Frederik [VerfasserIn]   i
Titel:Varying immunizations with plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics
Verf.angabe:Roland Frank, Michael Gabel, Kirsten Heiss, Ann-Kristin Mueller and Frederik Graw
Fussnoten:Das Pluszeichen ist im Titel hochgestellt ; Gesehen am 24.07.2018
Titel Quelle:Enthalten in: Frontiers in immunology
Jahr Quelle:2018
Band/Heft Quelle:9(2018) Artikel-Nummer 1137, 13 Seiten
ISSN Quelle:1664-3224
Abstract:Whole sporozoite vaccines (WSV) represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosage and frequency, we systematically analyzed intrasplenic and intrahepatic CD8+ T cell responses following varied immunizations of mice with radiation-attenuated sporozoites (RAS). By combining experimental data and mathematical modeling, our analysis indicates a reversing role of spleen and liver in the generation of protective liver-resident CD8+ T cells during priming and booster injections: While the spleen acts as a critical source compartment during priming, the increase in vaccine-induced hepatic T cell levels is likely due to local reactivation in the liver in response to subsequent booster injections. Higher dosing accelerates the efficient generation of liver-resident CD8+ T cells by especially affecting their local reactivation. In addition, we determine the differentiation and migration pathway from splenic precursors towards hepatic memory cells thereby presenting a mechanistic framework for the impact of various vaccination protocols on these dynamics. Thus, our work provides important insights into organ-specific CD8+ T cell dynamics and their role and interplay in the formation of protective immunity against malaria.
DOI:doi:10.3389/fimmu.2018.01137
URL:Kostenfrei: Verlag: http://dx.doi.org/10.3389/fimmu.2018.01137
 Kostenfrei: Verlag: https://www.frontiersin.org/articles/10.3389/fimmu.2018.01137/full
 DOI: https://doi.org/10.3389/fimmu.2018.01137
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1577887999
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