Th memory for interleukin-17 expression is stable in vivo

Eur J Immunol. 2008 Oct;38(10):2654-64. doi: 10.1002/eji.200838541.


Based on the memory for the re-expression of certain cytokine genes, different subsets of Th cells have been defined. In Th type 1 (Th1) and Th2 memory lymphocytes, the genes for the cytokines interferon-gamma and interleukin (IL)-4 are imprinted for expression upon restimulation by the expression of the transcription factors T-bet and GATA-3, respectively, and epigenetic modification of the cytokine genes. In Th17 cells, IL-17 expression is dependent on the transcription factors RORgammat and RORalpha. Here, we analyze the stability and plasticity of IL-17 memory in Th17 cells. We have developed a cytometric IL-17 secretion assay for the isolation of viable Th cells secreting IL-17. For Th17 cells generated in vitro, IL-17 expression itself is dependent on continued TGF-beta/IL-6 or IL-23 signaling and is blocked by interferon-gamma and IL-4 signaling. In response to IL-12 and IL-4, in vitro generated Th17 cells are converted into Th1 or Th2 cells, respectively. Th17 cells isolated ex vivo, however, maintain their IL-17 memory upon subsequent in vitro culture, even in the absence of IL-23. Their cytokine memory is not regulated by IL-12 or IL-4. Th17 cells generated in vivo are a stable and distinct lineage of Th cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cell Separation
  • Immunologic Memory*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Mice
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Interleukin-17
  • Interleukin-23
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma