TH2 lymphocytes secrete functional VIP upon antigen stimulation.

In addition to the peptidergic innervation, immune cells may also represent a source for VIP in the lymphoid organs. Previous studies reported increased VIP mRNA and protein expression in mitogen-stimulated B and T lymphocytes. To determine whether specific T cell subsets are responsible for VIP production, we derived TH1 and TH2 effector cell lines from T-cell receptor transgenic mice. TH1 and TH2 cells were stimulated with the specific (pigeon cytochrome C peptide) or nonspecific (ovalbumin) antigen presented by MHC class II compatible antigen-presenting cells. Upon stimulation with the specific antigen, TH2, but not TH1 cells express VIP mRNA and intracelllular VIP protein, as determined by Northern blots and FACS analysis. Supernatants harvested from antigen-stimulated TH2 cells contain secreted VIP, as determined by Elisa, and induce cAMP in HEK293 cells transfected with the specific VIP/PACAP receptor VPAC1. These results confirm that TH2, but not TH1 cells, express and secrete functional VIP following specific antigen stimulation. The release of VIP within the lymphoid microenvironment following antigenic stimulation provides a physiological basis for the immunoregulatory effects of VIP on neighboring immune cells, such as downregulation of macrophage activation, effects on lymphocyte migration, on antigen-induced T cell apoptosis, and on T cell differentiation.