Expression of α-AR Subtypes in T Lymphocytes and Role of the α-ARs in Mediating Modulation of T Cell Function

Abstract

Objectives: Previous work in our laboratory has shown that α-adrenoreceptors (α-ARs) and β-ARs exist on lymphocytes from functional profile, and that the receptors mediate the regulation of lymphocyte function by catecholamines. In the present study, we directly examined the expression of α-AR subtypes, α₁-AR and α₂-AR mRNAs, in T lymphocytes and explored the roles of the α-AR subtypes and intracellular signal transduction mechanisms linked to the receptors in mediating the modulation of T lymphocyte function. Methods: T lymphocytes from mesenteric lymph nodes of rats were purified by using a nylon wool column. Reverse transcription polymerase chain reaction was used to detect the expression of α₁-AR and α₂-AR mRNAs in the freshly isolated T cells and the mitogen concanavalin A (Con A)-activated lymphocytes. Colorimetric methylthiazoletetrazolium assay was employed to measure lymphocyte proliferation induced by Con A. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels in the Con A-stimulated lymphocyte culture supernatants were examined by enzyme-linked immunosorbent assay. Results: T cells expressed both α₁-AR and α₂-AR mRNAs. The expression of both α₁-AR and α₂-AR mRNAs was significantly higher in the Con A-activated lymphocytes than in the resting lymphocytes. Phenylephrine, a selective α₁-AR agonist, had no evident effect on lymphocyte proliferation nor on IFN-γ and IL-4 production induced by Con A. However, the selective α₂-AR agonist clonidine attenuated Con A-induced lymphocyte proliferation as well as IFN-γ and IL-4 production. The inhibited lymphocyte proliferation and IFN-γ and IL-4 production by clonidine were blocked by yohimbine, an α₂-AR antagonist. Either phospholipase C inhibitor U-73122 or protein kinase C inhibitor chelerythrine partially prevented the suppressive effect of clonidine on Con A-stimulated lymphocyte proliferation and IL-4 production. Conclusions: T lymphocytes express both α₁-ARs and α₂-ARs, but only the α₂-ARs participate in the suppressive modulation of lymphocyte proliferation and cytokine production in vitro. The inhibitory effect of α₂-AR stimulation on lymphocyte function is partially mediated via the phospholipase C-protein kinase C pathway.