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

FASEB J. 2002 May;16(7):727-9. doi: 10.1096/fj.01-0891fje. Epub 2002 Mar 26.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Lineage
  • Glucocorticoids / physiology*
  • Homeostasis
  • Lymphocyte Count
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Glucocorticoids
  • Receptors, Glucocorticoid