Phosphatidylinositol 3 Kinase Activity Is Not Essential for B7-1-Mediated Costimulation of Proliferation or Development of Cytotoxicity in Murine T Cells

It has been suggested that induction of phosphatidylinositol (PI) 3 kinase activity upon CD28 costimulation may contribute to CD28-mediated signaling. In this report, T cell stimulation by microspheres bearing coimmobilized anti-TCR mAb and purified B7-1 ligand was examined. This approach allows study of cosignaling mediated by CD28 interaction with its native ligand in the absence of potentially confounding contributions from other receptor-ligand interactions. For murine CD4⁺ CD8⁺ T cells, costimulation with B7-1 up-regulated PI3 kinase activity assayed in vitro, and this was blocked by treatment of the cells with wortmannin, a specific inhibitor of PI3 kinase, before stimulation. However, wortmannin failed to inhibit B7-1-dependent T cell proliferation or development of cytotoxicity in CD8⁺ cells. These results indicate that the enzymatic activity of PI3 kinase is not essential in the CD28-mediated signaling involved in the co-stimuiation of proliferation or induction of CTL activity in precursor CTL.