The Journal of Immunology, Vol 157, Issue 6 2243-2246, Copyright © 1996 by American Association of Immunologists

CUTTING EDGE

Phosphatidylinositol 3 kinase activity is not essential for B7-1- mediated costimulation of proliferation or development of cytotoxicity in murine T cells

HT Ni, MJ Deeths and MF Mescher
Center for Immunology, University of Minnesota, Minneapolis 55455, USA.

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+ and 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 costimulation of proliferation or induction of CTL activity in precursor CTL.

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