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

Gabel M, Baumann NS, Oxenius A, Graw F (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 10

Article Number: 1358

Journal Issue: JUN

DOI: 10.3389/fimmu.2019.01358

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 (1^st-expansion - contraction - 2^nd 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.

Authors with CRIS profile

Frederik Graw

Involved external institutions

Ruprecht-Karls-Universität Heidelberg

Germany (DE) Eidgenössische Technische Hochschule Zürich (ETHZ) / Swiss Federal Institute of Technology in Zurich

Switzerland (CH)

How to cite

APA:

Gabel, M., Baumann, N.S., Oxenius, A., & Graw, F. (2019). Investigating the dynamics of MCMV-specific CD8+ T cell responses in individual hosts. Frontiers in Immunology, 10(JUN). https://doi.org/10.3389/fimmu.2019.01358

MLA:

Gabel, Michael, et al. "Investigating the dynamics of MCMV-specific CD8+ T cell responses in individual hosts." Frontiers in Immunology 10.JUN (2019).

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