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.
Pazirandeh
Ahmad
A
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Novum, SE-141 86 Huddinge, Sweden.
Xue
Yintong
Y
Prestegaard
Tore
T
Jondal
Mikael
M
Okret
Sam
S
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D005938:Glucocorticoids / Q000502:physiology*; D006706:Homeostasis; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid