CD4+ cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs (Nat Immunol, 2011, doi:10.1028/ni.1996)

報告日期: 2011/03/22
報告時間: 15:10/16:00
報告學生: 周佳璇
講評老師: 謝奇璋

Full text:

CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs
Jie Sun, Haley Dodd, Emily K Moser, Rahul Sharma& Thomas J Braciale
Nature Immunology (6 February 2011) doi:10.1038/ni.1996 Article
Speaker: Chia-Hsuan Chou (周佳璇)
Commentator: Shieh, Chi-Chang K., M.D., Ph.D (謝奇璋醫師)
Time: 15:10-16:00
Place: Room 602
The host responses against viral infections include the production of many proinflammatory cytokines and chemokines for theclearance of the infections. However, the excessive inflammation, especially that induced by influenza virus infection in lung would cause acute lung injury and be life-threatening. IL-10 is a major anti-inflammatory cytokine. Previous reports show that CD8+ T cells contributed to a larger fraction of the IL-10 producing, and that IL-10+ CTL development required IL-27 and helper T cells. IL-27 played a synergistic role for the CD4+T cell–mediated induction of IL-10 by CTLs. The data indicated that the depletion of CD4+T cells severely impaired the production of IL-10, but not IFN-γ or tumor necrosis factor (TNF) by CTLs. IL-2 is one of the principal cytokines produced by CD4+T cells and has been shown to support expansion and differentiation of CTLs. IL-2 is therefore likely to be the primary molecule derived from CD4+T cells that provides help to CD8+T cells to drive the development of IL-10-producing CTLs. In this paper the authors further identified early IL-2 signaling was required to induce IL-10+ CTLs in vivo too. In addition, IL-2 and IL-27 were necessary for the development of IL-10-producing CTLs during influenza infection. They suggest that the induction of IL-10-producing CTLs by IL-27 likewise required the presence of IL-2, not just the synergy between IL-27 and CD4+T cell–derived IL-2 but also cooperatively induced the highly IL-10 mRNA expressions and IL-10 protein production by CD8+T cells. Finally, it was found that IL-2–IL-27 mediated induction of IL-10 production by CTLs in vitro was Blimp-1 dependent and that the regula­tion by Blimp-1 of IL-10 production by CTLs was cell intrinsic.   
Sun, J., Madan, R., Karp, C.L. & Braciale, T.J. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat. Med. 15, 277–284 (2009).