CD4⁺ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs

Sun, J. et al. 2011. Nat. Immunol. 12:327-334.

Student: Yi-Jui Chuang (莊宜叡)                                   Time:13:00-14:00, Jun. 8, 2011

Commentator: Dr. Chi-Chang Shieh (謝奇璋 博士)   Place: Room 601

Abstract

IL-10 is an important anti-inflammatory cytokine that can modulate excessive immune mediated injury. During influenza infection, antiviral CD8⁺ CTLs are major producer of IL-10 in the respiratory tract to fine-tune the extent of lung inflammation and injury [1]. However, the detail mechanism to drive the production of IL-10 by CTLs is still unknown. Previous study demonstrated that IL-27 induces the development of IL-10-producing CD4⁺ T cell [2]. This study shows that the development of IL-10⁺ CTLs was blocked in mice lacking of IL-27 or CD4⁺ T cell during influenza infection. IL-2 is a cytokine produced by CD4⁺ T cell and play an important role in expansion and differentiation of CTLs [3]. The authors used T cell-dendritic cell culture system to determine the role of IL-2 on the development of IL-10⁺ CTLs. IL-2 neutralization completely blocked the induction of IL-10⁺ CTLs. Il2ra^-/- CD8⁺ T cell transferred into influenza infected mice failed to produce IL-10. These data suggest that IL-27 and IL-2 are critical for stimulating IL-10⁺ CTLs during influenza infection. The mRNA level of Blimp-1 was higher in IL-10⁺ CTLs than in IL-10^-CTLs. Blimp-1, a transcriptional regulator for T effector cell differentiation, is known to be induced by IL-2 [4]. CD8⁺ T cells lacking Blimp-1 proliferated normally but failed to produce IL-10 in response to IL-2 and IL-27. Taken together, theses data suggest that CD4⁺ T cell-derived IL-2 cooperates with innate immune cell-derived IL-27 to amplify IL-10 production by CTLs through a Blimp-1 -dependent mechanism.

References

1.      Sun, J. et al. 2009. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat.Med. 15:277-284.

2.      Anderson, C. F. et al. 2010. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10:170-181.

3.      Belz, G.T. et al. 2010. Interleukin-2 tickles T cell memory. Immunity. 32:7-9.

4.       Martins, G. A. et al. 2006. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat. Immunol. 7:457-465.