In vivo modulation of the distribution of thymocyte subsets by female sex steroid hormones

Abstract

This study examined the effects of the principal ovarian steroids, 17 beta -estradiol (E) and progesterone (P), on the thymic structure and on the intrathymic development of T-cells. Adult female rats were ovariectomized (OVX) and treated for 13 days with physiological doses of either E or P; controls received an equivalent volume of vehicle. Ovariectomy produced a marked increase (vs, sham-operated controls) in thymus weight, which was associated with an increase in the volume and cellularity of both the medulla and cortex. Treatment of OVX rats with E reduced the thymic weight to value, which was significantly lower than that of sham-operated controls decreasing the volume of cortex below level in sham-OVX rats, and reversing the effect of ovariectomy on the volume of medulla. P only prevented the increases in thymus weight and cortical volume induced by OVX. However, unlike E, it had no discernable effect on the medullary volume. E treatment reduced the cellularity of the cortex and medulla to values, which were lower than those of sham-OVX rats, while P only reversed the effects of OVX on the cellularity of both the compartments. Ovariectomy also had a profound effect on the thymocyte profile, increasing the proportion of CD4(+)8(+)TCR alpha beta (-) cells and producing a corresponding decrease in the relative proportions of all TCR alpha beta (high) cell subsets. The decrease in the latter was opposed by treatment with E or P. However, the sensitivity of the less mature cells (except CD4(-)8(-)TCR alpha beta (-), the percentage of which was reduced by both hormones) to the two hormones differed. E reduced the relative proportion of CD4(-)8(+)TCR alpha beta (-), CD4(-)8(+)TCR alpha beta (low) and CD4(+) 8(+)TCR alpha beta (-) cells, while P increased the percentage of CD4(-) 8 +TCR alpha beta (low) cells. The results suggest that E anti P affect both the lymphoid and nonlymphoid compartments of the thymus, and that while P increases the volume of the nonlymphoid component of the medulla, E has the opposite effect. The finding that ovariectomy decreased while E and P increased the relative proportion of the most mature thymocytes, which include CD4(-)8(-)TCR alpha beta (high) cells that are believed to harbour potentially autoreactive cell clones, is particularly interesting and may relate to the high propensity of autoimmune diseases in females.