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.
Xin
Z
Z
Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
Tang
H
H
Ganea
D
D
D000818:Animals; D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D007376:Interleukin-2 / Q000037:antagonists & inhibitors*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000906:Antibodies; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate