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

Jie Sun, et al. 2009. Nature Medicine 15, 277-284

Speaker: Tzu-Hao Yeh (葉子豪)                                   Time: 15:10~16:00, Dec. 9, 2009

Commentator: Dr. Chun-Keung Yu (余俊強老師)       Place: Room 601

Abstract:

        Immune systems protect hosts from pathogen invasion, but hyperactivation of immune responses may cause pathogenic damage of hosts. The over-reactive immune responses can be prevented by some negative regulators, for example, the anti-inflammatory cytokine interleukin-10 (IL-10). IL-10 is majorly produced by immunosuppressive cells, such as regulatory T (Treg) cells and tolerogenic dendritic cells, and contributes to chronic viral infection. However, the production, cellular source and functional role of IL-10 in acute viral infection remain unclear. To clarify these issues, the authors use an animal model of acute respiratory infection with influenza viruses. Intranasal infection with sublethal dosage of influenza viruses triggers rapid and transient IL-10 production in respiratory tracks, with a similar kinetics as the production of a proinflammatory cytokine interferon-g (IFN-g). The IL-10 is exclusively produced from virus-responsive CD8⁺ and CD4⁺ T cells. Unexpectedly, these IL-10-producing T cells in lungs exhibit effector phenotypes as demonstrated by their co-expression of IFN-g, specific surface markers and the transcription factor T-bet. Massive production of IL-10 and IFN-g in the infected lungs requires both CD8⁺ and CD4⁺ T cells. Of note, blocking IL-10 signaling through neutralization of IL-10 receptor increases mortality of the virus-infected mice but exerts no effect on the virus loads. The lethal outcome is accompanied by elevated production of inflammatory cytokines and pulmonary infiltration of monocytes and neutrophils. Suppression of the exaggerated inflammatory responses by corticosteroid alleviates the lethal damage, suggesting that uncontrolled inflammation is a major cause of the lethality induced by IL-10 blockade. Taken together, IL-10 produced from effector T cells may play a critical role in prevention of inflammation-induced lung injury after influenza infection. In addition, reduction of local IL-10 may be potentially linked to severe pulmonary damage caused by highly pathogenic influenza viruses.

References:

1.          Couper, K.N., et al. IL-10: The Master Regulator of Immunity to Infection. J Immunol. 180, 5771-5777 (2008).

2.          O’Garra, A., et al. T_H1 cells control themselves by producing interleukin-10. Nat. Rev. Immunol. 7, 425–428 (2007).