title: Enhancement by vasoactive intestinal peptide of gamma-interferon production by antigen-stimulated type 1 helper T cells.
abstract: Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator in immune tissues that affects many T cell functions through two homologous high-affinity G-protein-coupled receptors, termed VIPR1 and VIPR2. Antigen-stimulated secretion of gamma-interferon (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, which express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-7) M VIP. Enhancement of IFN-gamma secretion reached a mean maximum of fourfold for VIP and threefold for a VIPR2-selective agonist, without any effect of a VIPR1-selective agonist. Secretion of IFN-gamma by PMA and ionomycin-stimulated clones of Th1 cells was not altered by VIP. Antigen-stimulated secretion of IFN-gamma by T cell receptor-transgenic, influenza hemagglutinin-specific, and cytokine-differentiated mouse lymph node Th1 cells, which also express VIPR1 and VIPR2, was enhanced by 10(-10) M to 10(-8) M VIP. Enhancement of IFN-gamma secretion increased to a maximum of 14-fold for VIP, 14-fold for the VIPR2-selective agonist, and 20-fold for the VIPR1-selective agonist. In contrast to VIP suppression of interleukin production and lack of effect on IFN-gamma production by T cells stimulated with anti-CD3 antibody or a mitogenic lectin, generation of IFN-gamma by antigen-stimulated T cells is enhanced significantly by physiological concentrations of VIP.
authors.affiliation: Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, California 94143-0711, USA.
authors.forename: N
authors.initials: N
authors.lastname: Jabrane-Ferrat
authors.forename: D
authors.initials: D
authors.lastname: Bloom
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Lo
authors.forename: S P
authors.initials: SP
authors.lastname: Sreedharan
authors.forename: C W
authors.initials: CW
authors.lastname: Turck
authors.forename: A E
authors.initials: AE
authors.lastname: Goetzl
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000941:Antigens; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*