EXPRESSION OF BCL-2, BCL-X, AND BAX AFTER T-CELL ACTIVATION AND IL-2 WITHDRAWAL

Bcl-2, bcl-x, and bar genes code for proteins that affect the suscepti bility of cells to apoptosis in general, the expression of bcl-2 or bc l-x inhibits apoptosis while bar promotes apoptosis. We examined the l evels of these proteins by immunoblotting in resting and activated T c ells and in thymocytes. Bcl-2 and Bar proteins vary coordinately, but Bcl-x varies independently: Bcl-2 and Bax are higher in splenic T cell s than in thymocytes, and their levels increase even more after T cell activation. In contrast, Bcl-x is almost undetectable in splenic T ce lls but is manyfold greater in thymocytes and in activated splenic T c ells. When CTLL-2 cells or activated T cells are starved of IL (IL-2), the level of Bcl-x but not Bcl-2 protein drops before the onset of ap optosis. Stable transfection of either bcl-2 or bcl-x expression plasm ids promotes the survival of CTLL-2 cells in the setting of IL-2 withd rawal. Over 70 to 90% of the transfected cells remain viable at 48 h a fter IL-2 withdrawal when all of the control transfected cells are apo ptotic. These findings suggest that a decrease in Bcl-x protein levels precedes apoptosis after IL-2 withdrawal in T cells and that transfec ted bcl-2 promotes survival after IL-2 withdrawal by functionally mask ing this drop in Bcl-x.