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

By Jie Sun, R. Madan, C. Karp, Thomas Braciale. Nature Medicine, 2009

649 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/0f4d1b1925987f27c63d7f04e30b1245350f7d19

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In Epidemiology

1. Nu Zhang
2. M. Bevan
3. A. García‐Sastre
4. R. Medina
5. E. Wherry
6. S. Mazmanian

In Immunology

1. Alexander Y. Rudensky
2. E. Wherry
3. A. Chaudhry
4. M. Bevan
5. Nu Zhang
6. D. Artis
7. P. Treuting
8. Robert Samstein

Citations in the corpus

• Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity (2012, background): “The immunregulatory cytokine IL-10 has been demonstrated to influ nce he antiviral immune re ponse (Bro k et al., 2006; M Kinstry et al., 2009; Sun et al., 2009) and expression of this c tokine can be modulated by commensal bacteria (Amaral et al., 2008; Mazmanian et al., 2008).”
• CD8+ T Cells: Foot Soldiers of the Immune System (2011, positive): “Fully differentiated effector CD8 + T cells produce large amounts of IL-10 at local infection sites in different viral infection models in the lung and brain (Palmer et al., 2010; Sun et al., 2009; Trandem et al., 2011).”
• Influenza A viruses: new research developments (2011, background): “However, a different study demonstrated that CD8 + effector T cells, by producing IL-10, could control the lung inflammation and injury that is induced during acute influenza virus infectio”
• Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans (2012, background): “Recently, both effector CD4 + and CD8 + T cells have been implicated in the control of pulmonary inflammation and limit excessive tissue damage by producing interleukin-10 (ref”
• Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection (2012, methodology): “IL-10-eGFP mice (Vert-X mice) have been described previously (Sun et al., 2009).”
• Expanding roles for CD4+ T cells in immunity to viruses (2012, background): “responses, but also, on the other hand, to exacerbated inflammation and immunopathology, which result in increased mortalit”
• Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation (2011, positive): “IL-10 has been implicated in limiting inflammation at environmental interfaces, in particular, in the gut and lung mucosa (Groux and Cottrez, 2003; Sun et al., 2009).”
• NeST, a long noncoding RNA, controls microbial susceptibility and epigenetic activation of the Ifng locus (2013, neutral): “CD8 + T cell populations are extremely heterogeneous (Davila et al., 2005; Joosten et al., 2007; Xystrakis et al., 2004); for example , the CD8 + T reg population is important in resolving inflammation and preventing autoimmunity (Frisullo et al., 2010; Sun et al., 2009; Trandem et al., 2011).”