Regulation of IL-17, IFN-gamma and IL-10 in human CD8(+) T cells by cyclic AMP-dependent signal transduction pathway

Cytokine. 1998 Nov;10(11):841-50. doi: 10.1006/cyto.1998.0375.


In the present study, the expression of interleukin 17 (IL-17) by human CD8(+) T lymphocytes and its regulation following PKA activation was determined and compared with that of interferon gamma (IFN-gamma) and IL-10. IL-17 mRNA was highly expressed in human CD8(+) T lymphocytes at least at the same level than in CD4(+) T cells that were isolated from peripheral blood mononuclear cells (PBMC). Expression of IL-17 mRNA in CD8(+) T cell was induced by prior activation of PBMC for 18 h with Ca2+ ionophore and phorbol myristate acetate (PMA). Furthermore, our results clearly showed that CD8(+) T cells are sensitive to elevation of cAMP and PKA activation pathway. Data demonstrated a significant inhibition of IL-17 as well as of IFN-gamma mRNA expression in CD8(+) T cells isolated from activated PBMC cultured in the presence of either dibutyryl cAMP (db-cAMP) or PGE2. In contrast, IL-10 mRNA expression was strongly enhanced in the same experimental conditions. The differential expression of IL-10 and IFN-gamma production in CD8(+) T cells was also observed at the protein level as it was measured by a double immunofluorescence technique and flow cytometry analysis. Taken together, these results provide evidence that human CD8(+) T cells are also the source of massive expression of IL-17, and that PKA plays a prominent role in the switch of CD8(+) T cells to a Th2 like profile and an inhibition of IL-17 expression, thus suggesting that the activation of cAMP signal transduction pathway may have consequences for the relative role of CD8(+) T cells in the immune and inflammatory process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / immunology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology
  • Lymphocyte Activation
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*


  • Interleukin-17
  • Interleukin-10
  • Interferon-gamma
  • Cyclic AMP