Differential effects of chronic propranolol treatment on the phenotypic profile of thymocytes from immature and adult rats

Abstract

To elucidate a putative role of beta-adrenoceptors in the modulation of intrathymic T-cell maturation, the expression of major differentiational antigene (CD4/CD8 and TCR alpha beta) on the thymocytes from both immature (aged 21 day at the beginning of the treatment) and adult (a,oed 75 days at the beginning of treatment) male rats subjected to a 15-day-long propranolol treatment (0.40 mg/100 g/day, s.c.) was analyzed by two- and one-color flow cytometry, respectively. Rats of matched age injected with saline served as controls. The propranolol treatment in immature but not adult rats caused a significant reduction in both the relative thymus weight and total thymocyte yield. In addition, a significant increase in the percentage of CD4(+)8(+) double-positive cells, with a proportional decrease in the relative proportion of CD4(+)8(-) single positive cells, was found in immature rats. In contrast, a slight but significant decrease in the percentage of CD4(+)8(+) cells with a parallel increase in the relative proportion of CD4+8- cells was found in adult rats. In both groups of rats, the percentage of TCR alpha beta(total) thymocytes was increased: in immature rats this was due to an increase in the percentage of TCR alpha beta(low) thymocytes, while in the adult rats it reflected a rise in the relative proportion of TCR alpha beta(high) cells. In conclusion, the study revealed that propranolol treatment in both immature and adult rats alters the relative proportion of CD4(+)8(+) and CD4(+)8(-) thymocytes, but in opposite fashion, and the data suggest that this treatment affects distinct fractions within the population of CD4(+)8(+) thymocytes with respect to expression of TCR alpha beta. The results also indicate that, regardless of rat sexual maturity, the development of thymocytes towards CD4(-)8(+) T-cells is relatively insensitive to long-lasting P-adrenoceptor blockade.