The Tetrapeptide AcSDKP, a Negative Regulator of Cell Cycle Entry, Inhibits the Proliferation of Human and Chicken Lymphocytes

The tetrapeptide AcSer-Asp-Lys-Pro (AcSDKP) is a physiological negative regulator of hematopoiesis in mammals. It acts by blocking the cell cycle entry of quiescent stem cells and progenitors. In the present study we report that AcSDKP blocks the proliferation of human as well as chicken lymphocytes. It inhibits by 25 to 40% the polyclonal mitogen- (phytohemagglutinin (PHA), pokeweed mitogen (PWM), or concanavalin A) or mixed lymphocyte reaction-induced proliferation of chicken lymphocytes. A comparable degree of inhibition was observed in human whole blood cultures stimulated by “T” (PHA) or “T and B” (PWM) mitogens. Our results obtained on two phylogenetically distant species show that AcSDKP reduces the lymphocyte proliferation probably by blocking or retarding entry into the cell cycle as previously demonstrated for hematopoietic progenitors and hepatocytes. Therefore, this endogenous, non-species-specific tetrapeptide may be involved in the regulation of immune response.