Investigating the dynamics of MCMV-specific CD8+ T cell responses in individual hosts

• Verfasst von: Gabel, Michael [VerfasserIn]
• Verfasst von: Baumann, Nicolas S. [VerfasserIn]
• Verfasst von: Oxenius, Annette [VerfasserIn]
• Verfasst von: Graw, Frederik [VerfasserIn]
• Titel: Investigating the dynamics of MCMV-specific CD8+ T cell responses in individual hosts
• Verf.angabe: Michael Gabel, Nicolas S. Baumann, Annette Oxenius and Frederik Graw
• E-Jahr: 2019
• Jahr: 19 June 2019
• Fussnoten: Das Pluszeichen ist im Titel hochgestellt ; Gesehen am 11.11.2019
• Titel Quelle: Enthalten in: Frontiers in immunology
• Ort Quelle: Lausanne : Frontiers Media, 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 10(2019) Artikel-Nummer 1358, 12 Seiten
• ISSN Quelle: 1664-3224
• DOI: doi:10.3389/fimmu.2019.01358
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CD8+ T cells
• Sach-SW: Individual dynamics
• Sach-SW: mathematical modeling
• Sach-SW: MCMV-infection
• Sach-SW: Memory inflation
• K10plus-PPN: 1681567113
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Infection by Cytomegalovirus (CMV) is characterized by the massive expansion and continued maintenance of CMV-specific CD8+ T cells for certain CMV-derived peptides. This phenomenon called "memory inflation" has made CMV a primary target for the generation of T cell based vaccine vectors against various diseases. However, many aspects concerning the generation and maintenance of the inflationary CD8+ T cell response still remain to be resolved. In this study, we combined experimental data and mathematical models to analyze the dynamics of circulatory inflationary CD8+ T cells within individual mice infected by MCMV. Obtaining frequent measurements on the number and frequency of CMV-specific CD8+ T cells up to 70 days post infection, we find that mathematical models assuming differing viral stimuli during acute infection and the inflationary phase provide a better description for the observed dynamics than models relying on similar viral stimuli during both phases. In addition, our analysis allowed a detailed quantification of the different phases of memory inflation within individual mice (1st-expansion - contraction - 2nd expansion/maintenance) indicating remarkable consistency of the timing of these phases across mice, but considerable variation in the size of the individual responses between mice. Our analysis provides a first step towards generating a mechanistic framework for analyzing the generation and maintenance of inflationary CD8+ T cells while accounting for individual heterogeneity. Extending these analyses by incorporating measurements from additional compartments and more prolonged sampling will help to obtain a systematic and quantitative understanding of the factors regulating the process of memory inflation.