Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts
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 agains...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-06-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01358/full |
id |
doaj-042f7a6ee5bd48a9bafd595be4d808e4 |
---|---|
record_format |
Article |
spelling |
doaj-042f7a6ee5bd48a9bafd595be4d808e42020-11-25T01:05:15ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01358458866Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual HostsMichael Gabel0Nicolas S. Baumann1Annette Oxenius2Frederik Graw3Center for Modelling and Simulation in the Biosciences, BioQuant-Center, Heidelberg University, Heidelberg, GermanyInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandCenter for Modelling and Simulation in the Biosciences, BioQuant-Center, Heidelberg University, Heidelberg, GermanyInfection 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01358/fullCD8+ T cellsMCMV-infectionmemory inflationmathematical modelingindividual dynamics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Michael Gabel Nicolas S. Baumann Annette Oxenius Frederik Graw |
spellingShingle |
Michael Gabel Nicolas S. Baumann Annette Oxenius Frederik Graw Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts Frontiers in Immunology CD8+ T cells MCMV-infection memory inflation mathematical modeling individual dynamics |
author_facet |
Michael Gabel Nicolas S. Baumann Annette Oxenius Frederik Graw |
author_sort |
Michael Gabel |
title |
Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts |
title_short |
Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts |
title_full |
Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts |
title_fullStr |
Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts |
title_full_unstemmed |
Investigating the Dynamics of MCMV-Specific CD8+ T Cell Responses in Individual Hosts |
title_sort |
investigating the dynamics of mcmv-specific cd8+ t cell responses in individual hosts |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-06-01 |
description |
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. |
topic |
CD8+ T cells MCMV-infection memory inflation mathematical modeling individual dynamics |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01358/full |
work_keys_str_mv |
AT michaelgabel investigatingthedynamicsofmcmvspecificcd8tcellresponsesinindividualhosts AT nicolassbaumann investigatingthedynamicsofmcmvspecificcd8tcellresponsesinindividualhosts AT annetteoxenius investigatingthedynamicsofmcmvspecificcd8tcellresponsesinindividualhosts AT frederikgraw investigatingthedynamicsofmcmvspecificcd8tcellresponsesinindividualhosts |
_version_ |
1725195304658010112 |