CD28 COSTIMULATION CAN PROMOTE T-CELL SURVIVAL BY ENHANCING THE EXPRESSION OF BCL-X(L)

T cell activation through the TCR can result in either cell proliferat ion or cell death. The role of costimulatory receptors in regulating T cell survival has not been defined. Here, we present data demonstrati ng that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 co stimulation to augment the production of IL-2, which acts as an extrin sic survival factor for T cells. In addition, CD28 costimulation augme nts the intrinsic ability of T cells to resist apoptosis. Although CD2 8 signal transduction had no effect on Bcl-2 expression, CD28 costimul ation was found to augment the expression of Bcl-x(L) substantially. T ransfection experiments demonstrated that this level of Bcl-x(L) could prevent T cell death in response to TCR cross-linking, Fas cross-link ing, or IL-2 withdrawal. These data suggest that an important role of CD28 costimulation is to augment T cell survival during antigen activa tion.