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 (Teff 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 Teff 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.
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We thank M. Hufford and T. Kim for critical comments and B. Small and S. Gill for excellent technical assistance. This work was supported by the US National Institutes of Health (grants AI-15608, HL-33391 and AI37293 to T.J.B. and AI057992 to C.L.K.).
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Sun, J., Madan, R., Karp, C. et al. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 15, 277–284 (2009). https://doi.org/10.1038/nm.1929
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