The influence of dexamethasone treatment on the lymphoid and stromal composition of the mouse thymus: a flowcytometric and immunohistological analysis |
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| Authors: | E van Vliet M Melis W van Ewijk |
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| Affiliation: | 1. MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK;2. Max Planck Institute of Molecular Cell Biology and Genetics, Technische Universität Dresden, Dresden 01307, Germany;1. Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan;2. Department of Traditional Chinese Medicine, Chang Gung University, Linkow, Taiwan;3. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan;2. Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, Sweden;3. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;1. Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, 8005-139 Faro, Portugal;2. Centre for Biomedical Research - CBMR, University of Algarve, Campus of Gambelas, Building 8, Room 2.22, 8005-139 Faro, Portugal;3. ABC - Algarve Biomedical Centre, 8005-139 Faro, Portugal;4. Division of Cardiovascular Medicine, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK;5. Cardiovascular Research Center, Massachusetts General Hospital, Charles River Plaza/CPZN 3200, 185 Cambridge Street, Boston, MA 02114-2790, USA;6. Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA;7. Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands;8. DSM Biotechnology Center, Alexander Fleminglaan 1, 2613 AX Delft, the Netherlands;1. Department of Immunology, University of Toronto, Toronto, ON, Canada;;2. Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;;3. Department of Medical Biophysics and, Toronto, ON, Canada;4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and;5. Peter Munk Cardiac Centre, Toronto General Research Institute, Toronto, ON, Canada;1. Departamento de Microbiología e Inmunología, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, CP 5800 Córdoba, Argentina;2. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Rivadavia 1917, Ciudad Autónoma de Buenos Aires, CP C1033AAJ, Argentina;3. Farmacognosia, Departamento de Farmacia, Universidad Nacional de Córdoba (IMBIV-CONICET), Ciudad Universitaria, Córdoba CP 5000, Argentina;4. Cátedra de Farmacología, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, CP 5800 Córdoba, Argentina |
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| Abstract: | The effect of injection of a range of doses of dexamethasone on the distribution of T-cell subpopulations and stromal cells in the thymus of BALB/c mice was investigated with flowcytometry and immunohistology. To this purpose we used monoclonal antibodies directed to the T-cell differentiation antigens Thy-1, T200, Lyt-1, Lyt-2, T4, MEL-14, and monoclonal antibodies directed to various classes of stromal cells. Injection of dexamethasone in increasing doses of 5-130 mg/kg body weight gradually leads to a depletion of the cortical thymocyte population, i.e., bright Thy-1 + ve, dull T-200 + ve, bright Lyt-2 + ve, and bright T4 + ve cells. These cortical cells are very dull MEL-14 + and express variable numbers of Lyt-1 molecules. Also the medulla is affected by dexamethasone although to a lesser extent. Dexamethasone injection at 130 mg/kg selects for a dull Thy-1 + ve, bright T-200 + ve, and bright Lyt-1 + ve medullary population. These cells are either T4 + ve Lyt-2-ve or T4-ve Lyt-2 + ve. Under these conditions, MEL-14 + ve cells were no longer present in the cortex but accumulated in medullary perivascular spaces. Staining of sequential sections showed that this particular subpopulation has a typical "helper" phenotype. This observation provides strong evidence that perivascular compartments are an exit pathway for emigrating T cells. The medullary population contains a phenotypically distinct, dexamethasone-sensitive subpopulation. This conclusion is based on two findings: 130 mg/kg dexamethasone depletes the thymus of all but 4% of the thymocytes, which form a much smaller subpopulation than the population of dull Thy-1 + ve cells (amounting to 15% of the total thymocytes). The medulla contains a subpopulation of dull Lyt-2 + ve cells, which are resistant to 20 mg/kg dexamethasone, but depleted by 130 mg/kg. Dexamethasone also has a severe effect on thymic nonlymphoid cells. Even at low doses, dexamethasone induces TR4 + ve cortical epithelial-reticular cells to become spherical ("nurse cell-like") structures, depleted of lymphoid cells. These stromal cells no longer express MHC antigens in a membrane-bound fashion. In contrast, the medullary epithelial cells appear morphologically unaffected even at a dexamethasone dose of 130 mg/kg. |
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