Prostaglandin E2 Enhancement of Interferon-γ Production by Antigen-Stimulated Type 1 Helper T Cells

Prostaglandin E2 (PGE2) is a potent mediator generated in immune tissues by cyclooxygenation of arachidonic acid. PGE2 affects T cell functions through four homologous G protein-coupled receptors termed EP1R, EP2R, EP3R, and EP4R that differ in tissue distribution and signaling. Antigen-evoked secretion of interferon-γ (IFN-γ) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, that express EP3Rs and EP4Rs, was enhanced a maximum of 3-fold by 10−10 to 10−8 M PGE2 and 2.5-fold each for the EP1R/EP3R-directed agonist sulprostone (10−8 and 10−7 M) and for the EP4R/EP3R/EP2R agonist misoprostol (10−9 M). Neither PGE2 nor the synthetic analogs affected secretion of IFN-γ by PMA plus ionomycin-stimulated clones of Th1 cells. Antigen-evoked secretion of IFN-gamma by influenza hemagglutinin-specific mouse lymph node Th1 cells, that also express EP3Rs and EP4Rs, was increased a maximum of 12-fold by 10−9 to 10−8 M PGE2, 14-fold by 10−9 M sulprostone, and 10-fold by 10−9 M misoprostol. Production of IFN-γ by either type of Th1 cell was not affected significantly by 10−6 M PGE2 alone. The generation of IFN-gamma by antigen-stimulated Th1 cells thus is significantly enhanced by physiologically relevant concentrations of PGE2.