The influence of dexamethasone treatment on the lymphoid and stromal composition of the mouse thymus: a flowcytometric and immunohistological analysis.
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.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects* / Q000276:immunology; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D006649:Histocompatibility Antigens; D018800:Thy-1 Antigens; D003907:Dexamethasone