Enhancement by vasoactive intestinal peptide of gamma-interferon production by antigen-stimulated type 1 helper T cells

Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator in immune tissues that affects many T cell functions through two homologous high-affi nity G-protein-coupled receptors, termed VIPR1 and VIPR2. Antigen-stimulate d secretion of gamma-interferon (IFN-gamma) by sperm whale myoglobin-specif ic Th1 cells of DBA/2 mouse I-E-d-restricted clones, which express VIPR1 an d VIPR2, was enhanced by 10(-10) M to 10(-7) M VIP. Enhancement of IFN-gamm a secretion reached a mean maximum of fourfold for VIP and threefold for a VIPR2-selective agonist, without any effect of a VIPR1-selective agonist. S ecretion of IFN-gamma by PMA and ionomycin-stimulated clones of Th1 cells w as not altered by VIP. Antigen-stimulated secretion of IFN-gamma by T cell receptor-transgenic, influenza hemagglutinin-specific, and cytokine-differe ntiated 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 su ppression of interleukin production and lack of effect on IFN-gamma product ion by T cells stimulated with anti-CD3 antibody or a mitogenic lectin, gen eration of IFN-gamma by antigen-stimulated T cells is enhanced significantl y by physiological concentrations of VIP.