Autonomous induction of proliferation, JNK and NF-kappa B activation in primary resting T cells by mobilized CD28

Induction of proliferation in primary resting T cells requires engagement o f both the antigen-specific TCR and the co-stimulatory receptor CD28. Here we report that CD28 functions as an autonomous mitogenic receptor which is mobilized by ICR signaling through cytoskeletal rearrangement. Shortcutting of TCR-dependent CD28 recruitment by stimulation with monoclonal antibodie s specific for mobilized CD28 results in maximum proliferation and IL-2 sec retion in primary resting T cells without activation of ZAP-70, a central c omponent of the TCR's signal transduction machinery. Engagement of mobilize d CD28 fully activates the c-Jun N-terminal kinase cascade and translocatio n of NF-kappa B, two key targets of signal integration in co-stimulation. W e propose a two-step activation model for co-stimulation in primary resting T cells in which antigen recognition recruits co-stimulatory receptors whi ch then autonomously transduce signals promoting T cell proliferation.