Both CD28 Ligands CD8O (B7-l) and CD86 (B7-2) Activate Phosphatidylinosito 3-Kinase, and Wortmannin Reveals Heterogeneity in the Regulation of T Cell IL-2 Secretion

摘要

In this report, the co-stimulatory signals provided by CD8O (B7-i) or CD86 (B7-2)were compared to CD28 ligation by mAb. We demonstrate that while both anti-CD3 and anti-CD28 antibodies induced activation of phosphoinositide (PI) 3-kinase, the kinetics of activation differed. Anti-CD28 produced a sustained activation of PI 3-kinase while anti-CD3 induced activation was transient. Both B7-i and B7-2 could induce prolonged activation of PI 3-kinase. The co-stimulatory effects of B7-1 and B7-2 were dependent on CD28 cross-linking, based on complete inhibition of PI 3-kinase activation by CD28 antibody Fab fragments. While Jurkat T cells co-stimulated with anti-CD3 and B7-1 or B7-2 secreted high levels of lL-2, there were distinct effects of anti-CD28 mAb and B7-1 or B7-2 on lL-2 secretion in conjunction with protein kinase C activation. To assess functional effects of CD28 ligation, pharmacologic inhibitors of PI 3-kinase were evaluated. In Jurkat cells, efficient inhibition of PI 3-kinase activation after B7-2 stimulation was achieved using wortmannin; however, we observed a surprising increase in lL-2 secretion after B7 or anti-CD28 stimulation.