Regulation of Differentiation and Function of Helper T Cells by Lymphocyte-Derived Catecholamines via α1- and β2-Adrenoceptors

Objective: Recently, we have reported that lymphocyte-derived endogenous catecholamines (CAs) facilitate a shift in the T helper (Th)1/Th2 balance towards Th2. The purpose of this study was to explore the involvement of adrenoreceptors (ARs) in Th differentiation and function modulation by lymphocyte-derived CAs. Methods: Lymphocytes were separated from the mesenteric lymph nodes of mice, stimulated with concanavalin A (Con A) and treated with pargyline, an inhibitor of CA degradation. Results: Pargyline downregulated the expression of Th1-relative factors, T-bet, interferon (IFN)-γ and interleukin (IL)-2, but upregulated the expression of Th2-relative factors, GATA-3, IL-4 and IL-10. Pargyline reduced the percentage of IFN-γ-producing CD4+ cells and the CD4+IFN-γ+/CD4+IL-4+ cell ratio, although it did not alter the proportion of IL-4-producing CD4+ cells. In addition, the percentage of CD4+CD26+ T cells and the CD4+CD26+/CD4+CD30+ cell ratio were also reduced in the pargyline-treated group. Furthermore, Con A-activated T cells treated with pargyline produced a lower level of IFN-γ and a higher level of IL-4 than the control group. All these effects were blocked by the α1-AR antagonist corynanthine or the β2-AR antagonist ICI 118551, but not by the α2-AR antagonist yohimbine or β1-AR antagonist atenolol. Conclusions: These results imply that lymphocyte-derived CAs promote polarization of differentiation and function towards Th2 cells and that this effect is mediated by α1-AR and β2-AR.