Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not T(H)2 cytokines

A region of the interleukin-2 (IL-2) promoter known as the RE/AP element is activated in concert by signals that originate from the T cell antigen rec eptor and the CD28 coreceptor. We show here that the serine-threonine kinas e Akt can provide a costimulatory signal for RE/AP activation that is indis tinguishable from the signal provided by CD28. This includes the ability of Akt, like antibodies to CD28, to synergize with protein kinase C theta (PK C-theta) in the induction of RE/AP. Retrovirus-mediated expression of activ ated Akt in primary T cells from CD28-deficient mice is capable of selectiv ely restoring production of IL-2 and interferon gamma, but not IL-4 or IL-5 . Our results provide evidence that CD28 costimulation of different cytokin es is mediated by discrete signaling pathways, one of which includes Akt.