Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10

Interleukin-10 is known to dampen immune responses and contribute to the persistence of chronic viruses and parasites. Thomas Braciale and his colleagues show in mice that the anti-inflammatory cytokine is produced, along with proinflammatory cytokines, by effector CD4 + and CD8 + T cells during an acute virus infection of the lung, thereby helping to regulate the extent of inflammatory lung damage in response to the virus. Activated antigen-specific T cells produce a variety of effector molecules for clearing infection but also contribute to inflammation and tissue injury. Here we report an anti-inflammatory property of antiviral CD8 + and CD4 + effector T cells (T eff cells) in the infected periphery during acute virus infection. We find that, during acute influenza infection, interleukin-10 (IL-10) is produced in the infected lungs in large amounts—exclusively by infiltrating virus-specific T eff cells, with CD8 + T eff cells contributing a larger fraction of the IL-10 produced. These T eff cells in the periphery simultaneously produce IL-10 and proinflammatory cytokines and express lineage markers characteristic of conventional T helper type 1 or T cytotoxic type 1 cells. Notably, blocking the action of the T eff cell–derived IL-10 results in enhanced pulmonary inflammation and lethal injury. Our results show that antiviral T eff cells exert regulatory functions—that is, they fine-tune the extent of lung inflammation and injury associated with influenza infection by producing an anti-inflammatory cytokine. We discuss the potential implications of these findings for infection with highly pathogenic influenza viruses.