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Social stress and T cell maturation in male rats: transient and persistent alterations in thymic function
Harald Engler1, Volker Stefanski
1Department of Animal Physiology, University of Bayreuth, D-95440 Bayreuth, Germany. engler.19@osu.edu
Insights
Social stress in male rats causes lasting changes to the thymus, reducing T cell production. Adrenal hormones are key, impacting immune cell numbers and function long-term.
Area of Science:
- Immunology
- Neuroendocrinology
- Stress Physiology
Background:
- Social stress is a significant environmental factor impacting physiological processes.
- The thymus is a primary lymphoid organ crucial for T cell development and immune competence.
- Understanding stress-induced immune system alterations is vital for public health.
Purpose of the Study:
- To investigate the effects of social stress on thymus function and cellularity in subordinate male rats.
- To identify the role of adrenal hormones in mediating stress-induced thymic changes.
- To assess the persistence and potential recovery of thymic alterations post-stress.
Main Methods:
- Induction of social stress through 24-h confrontation with a dominant male.
- Assessment of thymic apoptosis, proliferation, and thymic export via recent thymic emigrants (RTE).
- Evaluation of thymocyte response to Concanavalin A (ConA) stimulation.
- Pharmacological interventions including adrenalectomy (ADX) and RU486 treatment.
Main Results:
- Social stress significantly increased thymic apoptosis and decreased proliferation and thymic export.
- A reduction in recent thymic emigrants (RTE) and Concanavalin A (ConA) response was observed in stressed rats.
- Adrenalectomy (ADX) completely prevented stress-induced thymic dysfunction.
- Thymocyte reduction and diminished ConA response persisted for at least seven days post-stress.
Conclusions:
- Social stress profoundly disrupts thymus homeostasis, mediated primarily by adrenal-derived hormones.
- Long-lasting thymic atrophy following social stress may compromise peripheral T cell pool diversity.
- These findings highlight the significant impact of social stress on immune system regulation and function.
Abstract:
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.
