Enhanced glucocorticoid receptor signaling in T cells impacts thymocyte apoptosis and adaptive immune responses
| Autor: | Holger M. Reichardt, Denise Tischner, Kirsty McPherson, Jens van den Brandt, Stefan Wiehr, Katrien L. de Graaf, Fred Lühder, Robert Weissert, Ralf Gold, Thomas Herrmann |
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| Rok vydání: | 2007 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental T-Lymphocytes Apoptosis Autoimmunity Biology Jurkat cells Pathology and Forensic Medicine Animals Genetically Modified 03 medical and health sciences Jurkat Cells 0302 clinical medicine Glucocorticoid receptor Immune system Receptors Glucocorticoid Transduction Genetic Adrenal Glands medicine Animals Humans Receptor 030304 developmental biology 0303 health sciences Experimental autoimmune encephalomyelitis Cell Differentiation medicine.disease Rats Thymocyte Immunology Signal transduction 030217 neurology & neurosurgery Glucocorticoid medicine.drug Signal Transduction Regular Articles |
| Zdroj: | The American journal of pathology. 170(3) |
| ISSN: | 0002-9440 |
| Popis: | To study the effect of enhanced glucocorticoid signaling on T cells, we generated transgenic rats overexpressing a mutant glucocorticoid receptor with increased ligand affinity in the thymus. We found that this caused massive thymocyte apoptosis at physiological hormone levels, which could be reversed by adrenalectomy. Due to homeostatic proliferation, a considerable number of mature T lymphocytes accumulated in the periphery, responding normally to costimulation but exhibiting a perturbed T-cell repertoire. Furthermore, the transgenic rats showed increased resistance to experimental autoimmune encephalomyelitis, which manifests in a delayed onset and milder disease course, impaired leukocyte infiltration into the central nervous system and a distinct cytokine profile. In contrast, the ability of the transgenic rats to mount an allergic airway response to ovalbumin was not compromised, although isotype switching of antigen-specific immunoglobulins was altered. Collectively, our findings suggest that endogenous glucocorticoids impact T-cell development and favor the selection of Th2- over Th1-dominated adaptive immune responses. |
| Databáze: | OpenAIRE |
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