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

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. (C) 2001 Elsevier Science B.V. All rights reserved.