IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8+ T cells

Eur J Immunol. 2011 Nov;41(11):3351-60. doi: 10.1002/eji.201141629. Epub 2011 Oct 13.


The effector functions of CD8(+) T cells are influenced by tissue inflammatory microenvironments. IL-33, a member of the IL-1 family, acts as a danger signal after its release during cell necrosis. The IL-33/ST2 axis has been implicated in various Th2 responses. Its role in CD8(+) T-cell-mediated immune response is, however, not known. Here we find that type 1 cytotoxic T (Tc1) cells cultured in vitro unexpectedly express high levels of the IL-33 receptor ST2. Interestingly, the expression of ST2 in Tc1 cells is dependent on T-bet, a master Th1/Tc1 transcription factor. In addition, IL-33 enhances TCR-triggered IFN-γ production. IL-33 together with IL-12 can stimulate IFN-γ production in Tc1 cells. Moreover, IL-33 synergizes with IL-12 to promote CD8(+) T-cell effector function. The synergistic effect of IL-33 and IL-12 is partly mediated by Gadd45b. Together, these in vitro data establish a novel role of IL-33 in promoting effector type 1 adaptive immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / immunology
  • Antigens, Differentiation / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Separation
  • Cells, Cultured
  • Flow Cytometry
  • Interleukin-12 / immunology*
  • Interleukin-12 / metabolism
  • Interleukin-33
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction / immunology*


  • Antigens, Differentiation
  • Gadd45b protein, mouse
  • Il33 protein, mouse
  • Interleukin-33
  • Interleukins
  • Receptors, Antigen, T-Cell
  • Interleukin-12