ß2-adrenergic regulation of T lymphocites function (in vitro study).

The aim of our study was to establish the influence of ß2AR agonists and antagonists on Th1/Th2 subpopulation balance in intact and activated CD4+ T lymphocyte. Jurkat leukemic T cell line was used as a model for studying T cell activation conditions under the influence of ß2AR ligands. As follows from the results of our studies, after the influence of ß2AR agonist isoproterenol on intact Jurkat cells expression of IL-2 was not changed in comparison to control level. Under the PHA-stimulation level of IL-2 production in Jurkat cells increased significantly; isoproterenol caused decrease level of IL-2 expression in the PHA-stimulated Jurkat cells. Adding of ß2AR antagonist propranolol to the Jurkat cells pre-incubated with isoproterenol didn't change expression of IL-2. ß2AR antagonist propranolol induced slight increase of IL-2 expression in PHA-stimulated Jurkat cells pre-incubated with isoproterenol. Neither isoproterenol nor propranolol didn't change intensity of IL-10 expression in intact Jurkat cells. In the PHA-stimulated Jurkat cells level of IL-10 production decreased in comparison to control level. Isoproterenol induced sharp intensification of IL-10 expression in these cells. Propranolol prevented increase of IL-10 expression in the PHA-stimulated Jurkat cells pre-incubated with ß2AR agonist. It was concluded that ß2ARs in dose-dependent manner regulate cytokine profile in intact and mitogen activated CD4+ T lymphocyte and by this way induce dose-dependent alterations of lymphocyte proliferation and immune response. This indicated existence of a link among immune response and sympathetic nervous system activity.

[The role of neuroendocrine mediators in regulatory activity of T-cells].

The aim of the study was to establish the role of some neuroendocrine mediators (agonists and antagonists of ß-adrenergic receptors, progesterone) in regulating T-cells activity. Studies conducted on the culture of leukemiatransformed T-cells (Jurkat cells) (DSMZ-Deutshe Sammulung von Mikroorganismen und Zellkulturen (Germany)). Jurkat Cells (4 x 105 cells/ml) stimulated with 50 µg/ml fitogemaglutinin A (PHA) at 370С for 5 minutes and then incubated for 24 hours alone, or together with ß- adrenergic receptors agonist izopretonolom (at dose of 10-5 M, 10-6 M), an antagonist, propranolol (dose of 10-5 M, 10-6 M) and progesterone (dose 0,07 µl, 0,7 µl) added to the incubation medium. The viability of Jurkat cells was determined by MTT test. It was shown that ß-adlenoretseptors agonist, izoprotenol didn't affect the activity of mitochondrial dehydrogenases in intact and contributed to their low activation (12%) in the mitogen-activated Jurkat cells. ß-adrenergic receptors antagonist, propranolol, promotes a significant reduction in activity of mitochondrial dehydrogenases, and hence the viability of both intact (40-60%) and mitogen stimulated Jurkat cells (20-40%). Viability of intact Jurkat cells didn't change, and dose-dependently increased in PHA-stimulated Jurkat cells during progesterone exposure. It was concluded that viability of the T-cells and hence their functional activity is largely sensitive to the influence of the ß-adrenoceptor antagonists and progesterone. These data should be considered in the clinical application of appropriate drugs.