Varying immunizations with plasmodium radiation-attenuated sporozoites alter tissue-specific CD8+ T cell dynamics

• Verfasst von: Frank, Roland [VerfasserIn]
• Verfasst von: Gabel, Michael [VerfasserIn]
• Verfasst von: Heiß, Kirsten [VerfasserIn]
• Verfasst von: Müller, Ann-Kristin [VerfasserIn]
• Verfasst von: Graw, Frederik [VerfasserIn]
• 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
• DOI: doi:10.3389/fimmu.2018.01137
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577887999
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

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.