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Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza
The current influenza vaccine provides narrow protection against the strains included in the vaccine, and needs to be reformulated every few years in response to the constantly evolving new strains. Novel approaches are directed toward developing vaccines that provide broader protection by targeting...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861172/ https://www.ncbi.nlm.nih.gov/pubmed/27242779 http://dx.doi.org/10.3389/fimmu.2016.00165 |
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author | Zarnitsyna, Veronika I. Handel, Andreas McMaster, Sean R. Hayward, Sarah L. Kohlmeier, Jacob E. Antia, Rustom |
author_facet | Zarnitsyna, Veronika I. Handel, Andreas McMaster, Sean R. Hayward, Sarah L. Kohlmeier, Jacob E. Antia, Rustom |
author_sort | Zarnitsyna, Veronika I. |
collection | PubMed |
description | The current influenza vaccine provides narrow protection against the strains included in the vaccine, and needs to be reformulated every few years in response to the constantly evolving new strains. Novel approaches are directed toward developing vaccines that provide broader protection by targeting B and T cell epitopes that are conserved between different strains of the virus. In this paper, we focus on developing mathematical models to explore the CD8 T cell responses to influenza, how they can be boosted, and the conditions under which they contribute to protection. Our models suggest that the interplay between spatial heterogeneity (with the virus infecting the respiratory tract and the immune response being generated in the secondary lymphoid organs) and T cell differentiation (with proliferation occurring in the lymphoid organs giving rise to a subpopulation of resident T cells in the respiratory tract) is the key to understand the dynamics of protection afforded by the CD8 T cell response to influenza. Our results suggest that the time lag for the generation of resident T cells in the respiratory tract and their rate of decay following infection are the key factors that limit the efficacy of CD8 T cell responses. The models predict that an increase in the level of central memory T cells leads to a gradual decrease in the viral load, and, in contrast, there is a sharper protection threshold for the relationship between the size of the population of resident T cells and protection. The models also suggest that repeated natural influenza infections cause the number of central memory CD8 T cells and the peak number of resident memory CD8 T cells to reach their plateaus, and while the former is maintained, the latter decays with time since the most recent infection. |
format | Online Article Text |
id | pubmed-4861172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48611722016-05-30 Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza Zarnitsyna, Veronika I. Handel, Andreas McMaster, Sean R. Hayward, Sarah L. Kohlmeier, Jacob E. Antia, Rustom Front Immunol Immunology The current influenza vaccine provides narrow protection against the strains included in the vaccine, and needs to be reformulated every few years in response to the constantly evolving new strains. Novel approaches are directed toward developing vaccines that provide broader protection by targeting B and T cell epitopes that are conserved between different strains of the virus. In this paper, we focus on developing mathematical models to explore the CD8 T cell responses to influenza, how they can be boosted, and the conditions under which they contribute to protection. Our models suggest that the interplay between spatial heterogeneity (with the virus infecting the respiratory tract and the immune response being generated in the secondary lymphoid organs) and T cell differentiation (with proliferation occurring in the lymphoid organs giving rise to a subpopulation of resident T cells in the respiratory tract) is the key to understand the dynamics of protection afforded by the CD8 T cell response to influenza. Our results suggest that the time lag for the generation of resident T cells in the respiratory tract and their rate of decay following infection are the key factors that limit the efficacy of CD8 T cell responses. The models predict that an increase in the level of central memory T cells leads to a gradual decrease in the viral load, and, in contrast, there is a sharper protection threshold for the relationship between the size of the population of resident T cells and protection. The models also suggest that repeated natural influenza infections cause the number of central memory CD8 T cells and the peak number of resident memory CD8 T cells to reach their plateaus, and while the former is maintained, the latter decays with time since the most recent infection. Frontiers Media S.A. 2016-05-09 /pmc/articles/PMC4861172/ /pubmed/27242779 http://dx.doi.org/10.3389/fimmu.2016.00165 Text en Copyright © 2016 Zarnitsyna, Handel, McMaster, Hayward, Kohlmeier and Antia. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zarnitsyna, Veronika I. Handel, Andreas McMaster, Sean R. Hayward, Sarah L. Kohlmeier, Jacob E. Antia, Rustom Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title | Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title_full | Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title_fullStr | Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title_full_unstemmed | Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title_short | Mathematical Model Reveals the Role of Memory CD8 T Cell Populations in Recall Responses to Influenza |
title_sort | mathematical model reveals the role of memory cd8 t cell populations in recall responses to influenza |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861172/ https://www.ncbi.nlm.nih.gov/pubmed/27242779 http://dx.doi.org/10.3389/fimmu.2016.00165 |
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