On the role of CD8(+) T cells in determining recovery time from influenza virus infection
Author(s)
Type
Journal Article
Abstract
Myriad experiments have identified an important role for CD8+ T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behavior in a single coherent framework. Here, we introduce a mathematical model of influenza viral dynamics incorporating innate, humoral, and cellular immune components and explore its properties with a particular emphasis on the role of cellular immunity. Calibrated against a range of murine data, our model is capable of recapitulating observed viral kinetics from a multitude of experiments. Importantly, the model predicts a robust exponential relationship between the level of effector CD8+ T cells and recovery time, whereby recovery time rapidly decreases to a fixed minimum recovery time with an increasing level of effector CD8+ T cells. We find support for this relationship in recent clinical data from influenza A (H7N9) hospitalized patients. The exponential relationship implies that people with a lower level of naive CD8+ T cells may receive significantly more benefit from induction of additional effector CD8+ T cells arising from immunological memory, itself established through either previous viral infection or T cell-based vaccines.
Date Issued
2016-12-20
Date Acceptance
2016-12-02
Citation
Frontiers in Immunology, 2016, 7, pp.1-13
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
13
Journal / Book Title
Frontiers in Immunology
Volume
7
Copyright Statement
© 2016 Cao, Wang, Yan, McVernon, Xu, Heffernan, Kedzierska and McCaw. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) http://creativecommons.org/licenses/by/4.0/. 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.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000390064000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
influenza
viral dynamics
mathematical model
cellular immunity
recovery time
ADAPTIVE IMMUNE-RESPONSE
MATHEMATICAL-MODEL
VIRAL CLEARANCE
MEMORY
NAIVE
MICE
DYNAMICS
DIFFERENTIATION
STIMULATION
VACCINATION
Publication Status
Published
Article Number
ARTN 611
Date Publish Online
2016-12-20