Effects of altered glucocorticoid sensitivity in the T‐cell lineage on thymocyte and T‐cell homeostasis

The homeostatic regulation that controls total thymocyte and peripheral T‐cell numbers is not clearly understood. We describe here a direct hormonal influence of endogenous levels of glucocorticoids (GCs) on thymocyte and peripheral T‐cell homeostasis independent of indirect systemic effects of GCs. The results were obtained by generating transgenic mice with an altered GC sensitivity targeted to thymocytes and peripheral T cells by increasing or decreasing glucocorticoid receptor (GR) expression specifically in thymocytes and peripheral T cells. A twofold increase in GC sensitivity resulted in a major decrease in thymocyte number, affecting all subpopulations, although single‐positive CD8 + cells were less influenced. In the thymus, this was due to increased apoptosis in the organ, whereas proliferation of thymocyte populations was unaffected. In the periphery, a pronounced reduction in T‐cell number was seen, demonstrating an effect of endogenous GCs also on T‐cell homeostasis. The effects were confirmed in transgenic mice with reduced GR expression, which showed increased thymocyte and T‐cell numbers. Thus, our data demonstrate that physiological GC levels are directly involved in controlling the size of both thymocyte and T‐cell pools.