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 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.
Sun
Jie
J
Beirne B. Carter Center for Immunology Research, University of Virginia, 409 Lane Road, Charlottesville, Virginia 22908, USA.
Madan
Rajat
R
Karp
Christopher L
CL
Braciale
Thomas J
TJ
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D004285:Dogs; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000096:biosynthesis*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016753:Interleukin-10