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 negativ e regulator of hematopoiesis in mammals. It acts by blocking the cell cycle entry of quiescent stem cells and progenitors. In the present st udy 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 lymphoc ytes, A comparable degree of inhibition was observed in human whole bl ood 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 r e tarding entry into the cell cycle as previously demonstrated for hem atopoietic progenitors and hepatocytes. Therefore, this endogenous, no n-species specific tetrapeptide may be involved in the regulation of i mmune response. (C) 1996 Academic Press, Inc.