E prostanoid 2 (EP2)/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2

Immunology. 2006 Jul;118(3):343-52. doi: 10.1111/j.1365-2567.2006.02376.x.


Prostaglandin E2 (PGE2) is a lipid mediator that displays important immunomodulatory properties, such as polarization of cytokine production by T cells. Recent investigations have revealed that the effect of PGE2 on cytokine production is greatly influenced by external stimuli; however, it is unclear whether PGE2 plays a significant role in major histocompatibility complex-mediated antigen-specific T-cell responses via binding to one of four subtypes of E prostanoid (EP) receptor alone or in combination. In the present study, we sought to determine the effect of PGE2 on antigen-specific CD4+ T-cell responses in humans, especially in terms of receptor specificity. We used purified protein derivative (PPD) and Cry j 1 as T helper type 1 (Th1) and Th2-inducing antigens, respectively. We generated several different Cry j 1- and PPD-specific T-cell lines (TCLs). PGE2 significantly and dose-dependently inhibited the proliferation and subsequent production of interleukin-4 by Cry j 1-specific TCLs and of interferon-gamma by PPD-specific TCLs upon antigen stimulation. Administration of EP2 receptor agonist and EP4 receptor agonist suppressed these responses in an adenylate cyclase-dependent manner, while EP1 and EP3 receptor agonists did not. Messenger RNA for EP2, EP3 and EP4, but not EP1, receptors were detected in Cry j 1- and PPD-specific TCLs, and no differences in EP receptor expression were observed between them. Furthermore, PGE2 and EP2 receptor agonist significantly inhibited interleukin-5 and interferon-gamma production by peripheral blood mononuclear cells in response to Cry j 1 and PPD stimulation, respectively. These results suggest that PGE2 suppresses both Th1- and Th2-polarized antigen-specific human T-cell responses via a cAMP-dependent EP2/EP4-mediated pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adolescent
  • Adult
  • Allergens / immunology
  • Antigens, Plant
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Dinoprostone / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immune Tolerance / immunology
  • Immunity, Cellular
  • Male
  • Middle Aged
  • Plant Proteins / immunology
  • Receptors, Prostaglandin E / agonists
  • Receptors, Prostaglandin E / immunology*
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • T-Lymphocyte Subsets / immunology*
  • Tuberculin / immunology


  • Adenylyl Cyclase Inhibitors
  • Allergens
  • Antigens, Plant
  • Cry j I protein, Cryptomeria japonica
  • Cytokines
  • Epitopes, T-Lymphocyte
  • PTGER2 protein, human
  • PTGER4 protein, human
  • Plant Proteins
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Tuberculin
  • Dinoprostone