Noradrenaline synthesized locally in draining lymph node cells modulates CD4+ T-cell development in rat EAE model: a role for a1-adrenoceptor

Abstract

Introduction: It has been suggested that: i) noradrenaline synthesis in ,,adrenergic“ immune cells changes during development of EAE and multiple sclerosis and ii) noradrenaline influences EAE development through a1−adrenoceptor. To elucidate mechanisms standing behind this phenomenon, a1−adrenoceptor−mediated influence of draining lymph node (dLN) cell−derived noradrenaline on CD4+ T−cell response in dLNs from Dark Agouti rats of both sexes immunized for EAE was examined. Methods: Cells recovered from dLNs on 7th day post−immunization were examined for noradrenaline synthesis/content and a1B−adrenoceptor expression using HPLC and/or flow cytometry. Additionally, effects of prazosin (a1- AR blocker) on CD4+ T−cell proliferation, the frequency of IL−17+ CD4+ T−cells and regulatory (Foxp3+CD25+) CD4+ T−cells (Tregs), activational/maturational molecule expression on antigen presenting cells (APCs) and their cytokine profile in dLN cell culture were examined using flow cytometry and/or qRT−PCR/ELISA. Results: Irrespective of sex, conventional CD4+ T−cells and Tregs, and APCs from rat dLNs synthesized noradrenaline, while only Tregs and APCs expressed a1B-adrenoceptor. In myelin basic protein−stimulated dLN cell cultures from rats of both sexes prazosin increased Treg frequency and Foxp3 expression, but diminished co−stimulatory CD80 and CD86 molecule expression on APCs, thereby reducing CD4+ cell proliferation.