Critical requirement for 4‐1BBL for protection from severe but not mild respiratory Influenza A infection in mice

Abstract

In view of intensifying concerns about pandemic Influenza virus, there is considerable interest in the mechanisms that control respiratory Influenza virus infection. Here we sought to determine the importance of 4‐1BBL‐mediated costimulation during mild versus severe respiratory Influenza virus infection in mice. During infection with the mildly virulent Influenza A/HKx31 virus, regardless of route of infection or epitope studied, 4‐1BBL is completely dispensable for the primary CD8 T cell response. However, 4‐1BBL is required for maximal recall responses, previously attributed to a requirement for 4‐1BBL in the maintenance of T cell memory. In contrast, during primary intranasal infection with Influenza A/PR8, which leads to severe respiratory disease in mice, the absence of 4‐1BBL results in decreased CD8 T cell responses in the lung, increased viral load and increased mortality. Thus 4‐1BBL plays a key role in protective immunity in the respiratory tract during severe Influenza disease. These results show that costimulation requirements are greater during severe as compared to mild respiratory Influenza virus infection.