CD28-mediated activation of resting human T cells without costimulation of the CD3/TCR complex

Stimulation of resting human T cells by crosslinked CD28 monoclonal antibodies (mAb) induces some early signaling events but does not lead to IL-2 secretion and proliferation. The induction of these functions usually requires the delivery of additional signals such as that provided by costimulation of the T cell receptor (TCR). We analyzed the capacity of a panel of different CD28 mAb to induce cellular functions in purified human T cells. Two patterns of reactivity were observed. "Costimulatory" CD28 mAb like 9.3 required coengagement of the CD3/TCR complex for the induction of IL-2 gene transcription and proliferation. On the other hand, a "stimulatory" pathway could be defined by the use of the CD28 mAb BW 828, which triggered IL-2 synthesis, IL-2R expression, and proliferation without further requirement for additional stimuli. BW 828-induced proliferation was sensitive to inhibition by cyclosporin A and was mainly found in the CD4+CD45R0+ ("memory") T cell subset. These data suggest that T cell stimulation with mAb BW 828 defines a CD28-associated signaling pathway which leads to the induction of effector functions without the need for CD3/TCR coengagement. This pathway might play a role in antigen-independent activation and expansion of T cells.