Allergic diathesis in transgenic mice with constitutive T cell expression of inducible vasoactive intestinal peptide receptor

Vasoactive intestinal peptide (VIP) and its G-protein-coupled receptors (VP AC1 and VPAC2 Rs) are prominent in the immune system. In T cells, VPAC1 R i s expressed constitutively whereas VPAC2 R is induced only after stimulatio n of the T cell receptor (TCR) or exposure to some cytokines. VPAC1 R and V PAC2 R also transduce different effects of VIP on T cells. Constitutive exp ression of VPAC2 R selectively in CD4(+) T cells (helper-inducer Th cells) of transgenic (TG) C57BL/6 mice directed by the lck tyrosine kinase promote r is now shown to evoke production of more Th2-type interleukins 4 and 5, a nd less Th1-type interferon gamma after TCR activation. VPAC2 R TG mice con sequently have significant elevations of blood IgE, IgG1, and eosinophils. VPAC2 R TG mice also show increased IgE antibody responses, which mediate h eightened cutaneous allergic reactions, and have depressed delayed-type hyp ersensitivity. VIP enhancement of the ratio of Th2 cell to Th1 cell cytokin es thus evokes an allergic state in normally nonallergic mice, which sugges ts the possibility of neuropeptide contributions to immune phenotypic alter ations in human hypersensitivity diseases.