IRF4 Modulates CD8+ T Cell Sensitivity to IL-2 Family Cytokines

Su Huang, Yingjia Shen, Duy Pham, Li Jiang, Zheng Wang, Mark H. Kaplan, Guangjun Zhang, Jie Sun

Research output: Contribution to journalArticlepeer-review


IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription. As a consequence, IRF4-deficient CD8+ T cells show diminished sensitivity to IL-2, IL-15, and IL-7 treatment in vitro. Furthermore, we found that IRF4-deficient CD8+ T cells had lower expression of CD122 and CD127 in vivo during influenza virus infection. These data suggest that IRF4 regulates the sensitivity of CD8+ T cells to IL-2 family cytokines, which correlates with the diminished effector and memory CD8+ T cell responses in IRF4-deficient CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)92-100
Number of pages9
Issue number6
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


Dive into the research topics of 'IRF4 Modulates CD8+ T Cell Sensitivity to IL-2 Family Cytokines'. Together they form a unique fingerprint.

Cite this