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 (IL)-2 and IL-4 inducibility in a developmentally controlled manner. Although 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 interactions in the thymus could play an important role in T cell development. The 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 previously reported to inhibit IL-2 and IL-4 production, as well as the proliferation 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 proliferation of murine thymocytes stimulated through the TCR/CD3 receptor. VIP inhibited both IL-2 and IL-4 production, as well as the proliferation of murine thymocytes in a dose-dependent and specific manner. Structurally related peptides such as secretin or glucagon had little or no inhibitory activity. The intact VIP molecule was required for the inhibitory effect, since amino- or carboxy-terminal fragments did not inhibit IL-2 production. The inhibitory effect of VIP was observed for VIP additions up to 12 h after the initiation of the cultures, and incubations 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 thymus.