DIFFERENTIAL ACTIVITY OF DEXAMETHASONE ON IL-2-INDUCED, IL-4-INDUCED,OR IL-9-INDUCED PROLIFERATION OF MURINE FACTOR-DEPENDENT T-CELL LINES

Mouse helper T cell lines were developed that proliferate permanently without Ag and APCs in response to either IL-2, IL-4, or IL-9, three c ytokines whose receptors interact with the IL-2R gamma-chain for signa l transduction. Depending on the growth factor, a marked difference wa s observed regarding the ability of dexamethasone (DEX) to inhibit cel l proliferation. In three different cell lines, proliferation induced by IL-2 was completely arrested, while that supported by IL-9 was hard ly affected. With IL-4, proliferation was also maintained but less mar kedly than with IL-9. Although DEX was able to induce apoptosis in the se cells, the inhibition of IL-2-induced proliferation was not the res ult of apoptosis, as this process was equally antagonized by all three factors. Moreover, addition of IL-4 or IL-9 to cultures previously in cubated with IL-2 and DEX for several days restored cell proliferation . Finally, autonomous cell variants derived from the factor-dependent cell lines were still protected by IL-4 and IL-9 against growth inhibi tion by DEX. Together, these results indicate that growth stimulation in the presence of glucocorticoids and inhibition of apoptosis involve distinct aspects of cytokine activities.