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 (VPAC1 and VPAC2 Rs) are prominent in the immune system. In T cells, VPAC1 R is expressed constitutively whereas VPAC2 R is induced only after stimulation of the T cell receptor (TCR) or exposure to some cytokines. VPAC1 R and VPAC2 R also transduce different effects of VIP on T cells. Constitutive expression of VPAC2 R selectively in CD4+ T cells (helper-inducer Th cells) of transgenic (TG) C57BL/6 mice directed by the lck tyrosine kinase promoter is now shown to evoke production of more Th2-type interleukins 4 and 5, and less Th1-type interferon gamma after TCR activation. VPAC2 R TG mice consequently have significant elevations of blood IgE, IgG1, and eosinophils. VPAC2 R TG mice also show increased IgE antibody responses, which mediate heightened cutaneous allergic reactions, and have depressed delayed-type hypersensitivity. VIP enhancement of the ratio of Th2 cell to Th1 cell cytokines thus evokes an allergic state in normally nonallergic mice, which suggests the possibility of neuropeptide contributions to immune phenotypic alterations in human hypersensitivity diseases.