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

Nature Medicine volume 15, pages 277–284 (2009)Cite this article

Abstract

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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Figure 1: Influenza-specific T cells preferentially produce IL-10 and IFN-γ in the influenza-infected BALB/c lungs.
Figure 2: IL-10–producing CD8+ and CD4+ T cells are type 1 effectors.
Figure 3: Kinetics of IL-10–producing CD8+ and CD4+ Teff cells in vivo. BALB/c mice were infected with influenza.
Figure 4: Teff cells are the major source of IL-10 in vivo during influenza infection.
Figure 5: IL-10R blockade in vivo results in increased mortality and accelerated death during influenza infection.
Figure 6: IL-10R blockade leads to lethal pulmonary inflammation during influenza infection.

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Acknowledgements

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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Authors and Affiliations

  1. Beirne B. Carter Center for Immunology Research, University of Virginia, 409 Lane Road, Charlottesville, 22908, Virginia, USA

    Jie Sun & Thomas J Braciale

  2. Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, and the University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, 45229, Ohio, USA

    Rajat Madan & Christopher L Karp

  3. Departments of Microbiology and Pathology, University of Virginia, 409 Lane Road, Charlottesville, 22908, Virginia, USA

    Thomas J Braciale

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  1. Jie Sun
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  2. Rajat Madan
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Contributions

J.S. performed the experimental work and T.J.B. supervised the project. R.M. and C.L.K. provided Vert-X mice for the study. The manuscript was written by J.S. and T.J.B. All authors approved the final manuscript.

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Correspondence to Thomas J Braciale.

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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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