IL-4 regulates VIP receptor subtype 2 mRNA (VPAC2) expression in T cells in murine schistosomiasis

In murine schistosomiasis, granuloma T cells express VPAC2 mRNA, whereas there is none in splenocytes. This suggests that T cell VPAC2 mRNA is inducible. To address this issue, splenocytes from schistosome-infected mice were incubated with anti-CD3 to induce VPAC2 mRNA, which only appeared when cell cultures also contained anti-IL-4 mAb. Granuloma cells expressed VPAC2 mRNA. This natural expression decreased substantially when cells were cultured 3 days in vitro. However, granuloma cells cultured with anti-IL-4 mAb strongly expressed VPAC2 mRNA. IL-4 KO mice were examined to further address the importance of IL-4 in VPAC2 regulation. Splenocytes and dispersed granuloma cells from IL-4 KO animals had substantially more VPAC2 mRNA than those in wild-type controls. VPAC2 mRNA content decreased when cells were cultured with rIL-4. VPAC2 mRNA localized to CD4+ T cells. Th1 cell lines expressed VPAC2 mRNA much stronger than Th2 cells. Anti-IL-4 mAb increased VPAC2 mRNA expression in Th2 cells cultured in vitro. However, rIL-4 could not suppress VPAC2 mRNA expression in Th1 cells. Thus, VPAC2 is an inducible CD4+ T cell receptor, and IL-4 down-modulates VPAC2 mRNA expression in Th2 cells.