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 ki nase 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 wit h its native ligand in the absence of potentially confounding contribu tions from other receptor-ligand interactions. For murine CD4(+) and C D8(+) T cells, costimulation with B7-1 upregulated 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, H owever, wortmannin failed to inhibit B7-1-dependent T cell proliferati on or development of cytotoxicity in CD8(+) cells, These results indic ate that the enzymatic activity of PI3 kinase is not essential in the CD28-mediated signaling involved in the costimulation of proliferation or induction of CTL activity in precursor CTL.