Phosphatidyl inositol hydrolysis after CD3 binding in human peripheral blood T cells: Inhibition by prostaglandin E 2

Abstract

Hydrolysis of phosphatidyl inositol-4,5-biphosphate, leading to generation of inositol phosphates (IPs), occurs after crosslinking CD3 antigens on the surface of murine and human T-cell lines and clones, and is thought to represent a basic mechanism of signal transduction after antigen receptor binding. Previous investigators have had difficulty demonstrating this phenomenon using human peripheral blood T-cells. In this paper we demonstrate significant IP generation after anti-CD3 stimulation of human peripheral blood lymphocytes and T-cells. The amount of IP generation is less and considerably more variable than what is obtained using a T-cell line. Also, exposure to ammonium chloride in the E-rosetting procedure totally inhibits IP generation, perhaps explaining previous unsuccessful attempts. Finally, prostaglandin E2 and other agents that raise cyclic AMP inhibit IP generation by anti-CD3 antibodies in human T-cells and a T-cell line.