VASOACTIVE-INTESTINAL-PEPTIDE INHIBITS INTERLEUKIN (IL)-2 AND IL-4 PRODUCTION IN MURINE THYMOCYTES ACTIVATED VIA THE TCR CD3 COMPLEX/

During their development in the thymus, T cells acquire interleukin (I L)-2 and IL-4 inducibility in a developmentally controlled manner. Alt hough the role of IL-2 and IL-4 in T cell development is still unclear , several reports indicated that IL-2/IL-2R and IL-4/IL-4R interaction s in the thymus could play an important role in T cell development. Th e presence of vasoactive intestinal peptide (VIP)-immunoreactive cells and nerve fibers in the thymus suggests the possible local release of the neuropeptide in the thymic microenvironment. VIP has been previou sly reported to inhibit IL-2 and IL-4 production, as well as the proli feration of mitogen- or antigen-stimulated peripheral T cells. Here we report on the effect of VIP on IL-2 and IL-4 production by and prolif eration of murine thymocytes stimulated through the TCR/CD3 receptor. VIP inhibited both IL-2 and IL-4 production, as well as the proliferat ion of murine thymocytes in a dose-dependent and specific manner. Stru cturally related peptides such as secretin or glucagon had little or n o inhibitory activity. The intact VIP molecule was required for the in hibitory effect, since amino- or carboxy-terminal fragments did not in hibit IL-2 production. The inhibitory effect of VIP was observed for V IP additions up to 12 h after the initiation of the cultures, and incu bations longer than 3 h were required for maximum inhibitory effects. Through its downregulatory effect on IL-2 and IL-4 production, locally released VIP could potentially affect T cell development within the t hymus.