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FASEB J. 2002 May;16(7):727-9. Epub 2002 Mar 26.

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

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  • 1Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Novum, SE-141 86 Huddinge, Sweden.

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.

PMID:
11923224
[PubMed - indexed for MEDLINE]
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