Publication:

Accessory cell-derived IL-12 and prostaglandin E2 determine the IFN-gamma level of activated human CD4+ T cells (1996)

Author(s): Hilkens CM, Snijders A, Vermeulen H, van der Meide PH, Wierenga EA, Kapsenberg ML

  • : Accessory cell-derived IL-12 and prostaglandin E2 determine the IFN-gamma level of activated human CD4+ T cells

Abstract: IL-12 and PGE2 are two immunomodulators produced by accessory cells (AC) in response to various stimuli. IL- 12 enhances IFN-gamma production by activated CD4+ T cells, whereas PGE2 inhibits the secretion of this cytokine. Because these AC-derived factors exert clearly opposite modulatory effects on IFN-gamma production, we examined 1) the net-IFN-gamma production of CD4+ T cells, stimulated in the presence of both IL-12 and PGE2, 2) the susceptibility of activated CD4+ T cells in time by adding these modulators at different timepoints after stimulation, and 3) the relative contributions of AC-derived IL-12 and PGE2 to IFN-gamma levels by stimulating CD4+ T cells in the presence of LPS-activated monocytes and inhibitors of PGE2 or IL-12. Here, we demonstrate that 1) IL-12 and PGE2 do not abrogate the modulatory action of each other and that the net-IFN-gamma production is determined by their concentration ratio, 2) T cells become insensitive to PGE2, whereas susceptibility to IL-12 is retained after activation, and 3) activated monocytes potently modulate IFN-gamma levels of stimulated CD4+ T cells via release of IL-12 and PGE2. The relative contributions of these AC-derived factors shift in time, due to different production kinetics, from a dominant IL-12 effect to a mixed IL-12/PGE2 effect. Because the net IFN-gamma production of CD4+ T cells is largely determined by the ratio of IL-12 and PGE2 at the timepoint of T cell activation, an imbalance in the production of these immunomodulators may, therefore, lead to immunologic dysfunction.

Notes: 0022-1767 Journal Article

  • Short Title: Accessory cell-derived IL-12 and prostaglandin E2 determine the IFN-gamma level of activated human CD4+ T cells
  • Date: 01-03-1996
  • Journal: Journal of Immunology
  • Volume: 156
  • Issue: 5
  • Pages: 1722-1727
  • Publisher: American Association of Immunologists
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Adjuvants, Immunologic/pharmacology Antigen-Presenting Cells/*metabolism CD4-Positive T-Lymphocytes/*drug effects/immunology Clone Cells Dinoprostone/*biosynthesis/*pharmacology Human Interferon Type II/analysis/antagonists & inhibitors/*drug effects Interleukin-12/*biosynthesis/pharmacology Kinetics Lymphocyte Activation/*drug effects Monocytes/metabolism Support, Non-U.S. Gov't

Staff

Dr Catharien Hilkens
Reader in Immunotherapy