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 14 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 and 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.
Leposavić
G
G
Immunology Research Center Branislav Jankovic, Institute for Immunology and Virology Torlak, Yugoslavia. leposa@afrodita.rcub.bg.ac.yu
Obradović
S
S
Kosec
D
D
Pejcić-Karapetrović
B
B
Vidić-Danković
B
B
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011374:Progesterone; D004958:Estradiol