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

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 Teff cells, with CD8(+) Teff cells contributing a larger fraction of the IL-10 produced. These Teff 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 Teff 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.