Differential effects of dexamethasone on the thymus and spleen: alterations in programmed cell death, lymphocyte subsets and activation of T cells.
The kinetics of DEX-induced changes in lymphocytes from the thymus and spleen of normal mice were examined in relation to cell numbers, programmed cell death (PCD), in vitro proliferative response to anti-CD3 antibodies or Con-A, and changes in lymphocyte subsets by flow cytometry. The above aspects were examined at 48, 24, 18, and 3 h after a single intraperitoneal injection of DEX. Profound reduction of thymocyte numbers was noticed particularly at 48 (74-84%) and 24 (43-55%) h after DEX administration. PCD of thymocytes was not detectable at 48 h, marginally detectable at 24 h, markedly evident at 18 h, and minimally detectable at 3 h pi of DEX. PCD in splenic lymphocytes of DEX-treated mice was not clearly evident at these time points. Thymocytes from mice exposed to DEX (48 or 24 h) proliferated vigorously when cultured in the presence of anti-CD3 or Con-A, thereby suggesting that the remaining thymocytes can transduce activation signals. In contrast, splenic lymphocytes from the same animals responded poorly to these stimulants. Flow cytometric studies revealed that there was a marked increase in number of thymocytes expressing CD3+ (4-6 fold) and alpha beta TCR+ (2-7 fold) surface molecules. On the other hand, no major changes in CD3+ or alpha beta TCR+ cells were noticed in the spleen of DEX-treated mice. Although the total numbers of cells expressing heat stable antigen, M1/69, were not markedly altered after DEX treatment, the fluorescent intensity profile was modified. There were no remarkable changes in CD45RB+ cells in these mice. CD44+ cells were not decreased in DEX-treated thymocytes or splenic lymphocytes. Our results suggest that DEX has differential effects on the thymus and the spleen.
Ahmed
S A
SA
Department of Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Sriranganathan
N
N
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D051927:CD24 Antigen; D017252:CD3 Complex / Q000276:immunology; D002352:Carrier Proteins / Q000187:drug effects; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology*; D005434:Flow Cytometry; D018960:Hyaluronan Receptors; D017493:Leukocyte Common Antigens / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects; D013154:Spleen / Q000166:cytology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; D017252:CD3 Complex; D002352:Carrier Proteins; C497890:Cd24a protein, mouse; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D003907:Dexamethasone; D004247:DNA; D017493:Leukocyte Common Antigens