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Glucocorticoids in T cell development and function*
J D Ashwell1, F W Lu, M S Vacchio
1Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. jda@Box-j.nih.gov
Annual Review of Immunology
|June 3, 2000
Summary
Glucocorticoids regulate T cell function by binding the glucocorticoid receptor (GR). These hormones impact T cell development, apoptosis, and immune suppression, with local production in the thymus influencing thymocyte selection.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoids are lipophilic compounds binding intracellular receptors (GR) to regulate gene transcription.
- Glucocorticoids are known for immunosuppression in peripheral T cells by inhibiting gene expression.
- They also influence T helper (Th) cell lineage development and T cell apoptosis.
Purpose of the Study:
- To elucidate the multifaceted roles of glucocorticoids in T cell biology.
- To investigate the impact of glucocorticoids on T cell development and function, including apoptosis and lineage commitment.
- To explore the proposed role of locally produced thymic glucocorticoids in thymocyte selection.
Main Methods:
- Review of existing literature on glucocorticoid effects on T cells.
- Analysis of in vitro and in vivo studies concerning T cell development.
- Discussion of proposed mechanisms involving GR signaling and gene transcription regulation.
Main Results:
- Glucocorticoids inhibit the expression of activation-induced genes in peripheral T cells, leading to immunosuppression.
- They promote Th2 cell generation and inhibit activation-induced T cell apoptosis via downregulation of fasL.
- Glucocorticoids induce apoptosis in thymocytes (CD4(+)CD8(+)) and may regulate thymocyte selection by altering TCR signaling thresholds.
Conclusions:
- Glucocorticoids play critical roles in T cell immunosuppression, apoptosis, and lineage development.
- Local glucocorticoid production within the thymus is proposed to be crucial for normal thymocyte development and selection.
- Further research using tissue-specific GR-deficient models is needed to fully understand glucocorticoid actions on T cell development and function.