Thymopoiesis following chronic blockade of beta-adrenoceptors

Abstract

The present study was undertaken in order to further clarify putative role of the adrenergic innervation in the regulation of the intrathymic T-cell maturation. For this purpose adult male DA rats were subjected to either 4-day- or 16-day-long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte proliferative and apoptotic index, was assessed in these animals by flow cytometric analysis. Propranolol treatment, in spite of duration, increased both the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated controls). In 4-day-treated animals the thymus cellularity and thymus weight remained unaltered, while in 16-day-treated rats the values of both of these parameters were reduced (since increase in the thymocyte apoptotic index overcame that in the proliferative index). The treatments of both durations affected the thymocyte phenotypic profile in a similar pattern, but the changes were more pronounced in rats exposed to the treatment of longer duration. The relative proportion of the least mature CD4-8- double negative (DN) TCRalphabeta(-) cells was increased, those of thymocytes at distinct differentiational stages on the transitional route to the CD4+8+ double positive (DP) TCRalphabeta(low) stage decreased (all subsets of TCRalphabeta(-) in both groups of rats, and those. with low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or unaltered (all subsets of TCRalphabeta(low) cells in 4-day-treated rats). Furthermore, the percentage of CD4+8+ DP TCRalphabeta(low) cells was significantly elevated, as well as those of the most mature CD4+8-TCRalphabeta(high) and CD4-8+TCRalphabeta(high) cells (the increase in the percentage of former was much more conspicuous than that of the latter), while the relative proportion of their direct detectable precursors (CD4+8+ DP TCRalphabeta(high)) Was reduced. Thus, the present study: i) further supports notion of pharmacological manipulation of adrenergic action as an efficient means in modulation of the T-cell development, and hence T-cell-dependent immune response, and ii) provides more specific insight into T-cell maturation sequence point/s particularly sensitive to beta-adrenoceptor ligand action.