Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts
Autor: | Gabel, Michael, Baumann, Nicolas S., Oxenius, Annette, Graw, Frederik |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
lcsh:Immunologic diseases. Allergy
Muromegalovirus MCMV-infection individual dynamics Immunology Epitopes T-Lymphocyte T-Cell Antigen Receptor Specificity CD8-Positive T-Lymphocytes Lymphocyte Activation CD8+ T cells Models Biological Mice Immunology and Allergy Animals Antigens Viral memory inflation Original Research CD8(+) T cells mathematical modeling Herpesviridae Infections Viral Load Host-Pathogen Interactions Virus Activation lcsh:RC581-607 Immunologic Memory Algorithms |
Zdroj: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology, 10 Frontiers in Immunology |
ISSN: | 1664-3224 |
DOI: | 10.3389/fimmu.2019.01358/full |
Popis: | 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 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. Frontiers in Immunology, 10 ISSN:1664-3224 |
Databáze: | OpenAIRE |
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