Broad programming by IL-2 receptor signaling for extended growth to multiple cytokines and functional maturation of antigen-activated T cells

Coincident production of IL-2 and induction of high-affinity IL-2R upon TCR engagement has precluded a clear distinction for the biological outcome of signaling through TCR/costimulatory molecules vs the IL-2R, Using a novel transgenic mouse on the IL-2R beta (-/-) genetic background, this study has separated the relative outcome of signaling through the TCR and IL-2R, We show that stimulation through the TCR and CD28 or CD40 ligand directly lead s to T cell activation and several rounds of proliferation in an IL-2-indep endent fashion. However, this stimulation is insufficient for extended T ce ll growth to multiple cytokines or differentiation into CTL or IFN-gamma -s ecreting effector T cells. IL-2 is required for these functions in part by regulation of cyclin D3 and granzyme B, Somewhat less efficiently, IL-4 sti mulation of these transgenic T cells redundantly rescued many of these acti vities, These data demonstrate a fundamental requirement for IL-2 and perha ps other common gamma -chain-dependent cytokines to promote selective gene expression by Ag-activated T cells for their subsequent growth and differen tiation into effector T lymphocytes.