Investigating the Dynamics of MCMV-Specific CD8 + T Cell Responses in Individual Hosts

• Published in: Frontiers in immunology Vol. 10; p. 1358
• Main Authors: Gabel, Michael, Baumann, Nicolas S, Oxenius, Annette, Graw, Frederik
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.06.2019
• Subjects: CD8+ T cells; Immunology; individual dynamics; mathematical modeling; MCMV-infection; memory inflation; MCMV-infection; mathematical modeling; CD8+ T cells; individual dynamics; memory inflation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01358

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 (1 -expansion - contraction - 2 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 toward 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.