On the role of $\rm CD8^+$ T cells in determining recovery time from influenza virus infection

TL;DR

This study develops a comprehensive mathematical model of influenza viral dynamics highlighting the critical role of CD8+ T cells in reducing recovery time, supported by experimental and clinical data.

Contribution

The paper introduces a new integrated immune response model that accurately reproduces viral kinetics and reveals a robust exponential relationship between CD8+ T cell levels and recovery time.

Findings

Model recapitulates diverse viral kinetic behaviors.

Higher effector CD8+ T cell levels significantly shorten recovery time.

Clinical data supports the predicted exponential relationship.

Abstract

Myriad experiments have identified an important role for $\rm CD8^+$ 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 behaviour in a single coherent framework. Here, we introduce a mathematical model of influenza viral dynamics incorporating all major immune components (innate, humoral and cellular) 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 $\rm CD8^+$ T cells and recovery time, whereby recovery time rapidly decreases to a fixed minimum recovery time with an increasing level of effector $\rm CD8^+$ T cells. We find support for this relationship in recent clinical data from influenza A(H7N9) hospitalised patients. The exponential relationship implies that people with a lower level of naive $\rm CD8^+$ T cells may receive significantly more benefit from induction of additional effector $\rm CD8^+$ T cells arising from immunological memory, itself established through either previous viral infection or T cell-based vaccines.