DIFFERENTIAL-EFFECTS OF DEXAMETHASONE ON THE THYMUS AND SPLEEN - ALTERATIONS IN PROGRAMMED CELL-DEATH, LYMPHOCYTE SUBSETS AND ACTIVATION OFT-CELLS

The kinetics of DEX-induced changes in lymphocytes from the thymus and spleen of normal mice were examined in relation to cell numbers, prog rammed cell death (PCD), in vitro proliferative response to anti-CD3 a ntibodies or Con-A, and changes in lymphocyte subsets by flow cytometr y. The above aspects were examined at 48, 24, 18, and 3 h after a sing le intraperitoneal injection of DEX. Profound reduction of thymocyte n umbers was noticed particularly at 48 (74-84%) and 24 (43-55%) h after DEX administration. PCD of thymocytes was not detectable at 48 h, mar ginally detectable at 24 h, markedly evident at 18 h, and minimally de tectable al 3 h pi of DEX. PCD in splenic lymphocytes of DEX-treated m ice 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 remaini ng thymocytes can transduce activation signals. In contrast, splenic l ymphocytes 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-t reated mice. Although the total numbers of cells expressing heat stabl e antigen, M1/69, were not markedly altered after DEX treatment, the f luorescent intensity profile was modified. There were no remarkable ch anges in CD45R(B)(+) cells in these mice. CD44(+) cells were not decre ased in DEX-treated thymocytes or splenic lymphocytes. Our results sug gest that DEX has differential effects on the thymus and the spleen.