Social stress and T cell maturation in male rats: transient and persistent alterations in thymic function.

The present study demonstrates that social stress in subordinate male rats resulting from a 24-h confrontation with a dominant male opponent caused not only transient but also persistent alterations in the function and the cellular composition of the thymus. The investigation of regulation processes maintaining tissue homeostasis in the thymus showed a significant increase in apoptosis, a decrease in cellular proliferation and a decrease in thymic export as indicated by a reduction in the number of recent thymic emigrants (RTE) in the peripheral blood. The proliferative response of mature thymocytes to Concanavalin A (ConA) was also significantly reduced in socially defeated rats. Adrenalectomy (ADX) completely abolished the stress-associated alterations in thymic function whereas a decrease in total thymocyte numbers was still evident in defeated animals treated with the glucocorticoid type-II receptor antagonist RU486. The significant reduction in total thymocytes and the diminished proliferative response to ConA persisted for at least seven days after stressor cessation. An enhanced proliferative activity at this point of time may represent a beginning regeneration of thymic tissue after stress. Taken together, our studies show that social stress profoundly disturbs tissue homeostasis in the thymus and suggest that adrenal-derived hormones play a central role in mediating this effect. The strong positive relationship between total thymocyte numbers and peripheral RTE numbers and the long-lasting atrophy of the thymus in defeated animals may suggest negative consequences for the heterogeneity of naïve T cells in the peripheral T cell pool after social stress.