Differential regulation of γ and δ T cell antigen receptor gene expression by phorbol esters and Ca²⁺ ionophores in the acute lymphocyte leukemia DND41 cell line

Abstract

We have investigated the role of two signal transduction pathways on the regulation of the γ and δ T cell antigen receptor (TcR) gene expression, in the acute lymphocytic leukemic cell line DND41. Protein kinase C (PKC) activation, and intracellular free Ca2+ mobilization, initiated by phorbol esters and calcium ionophores, respectively, not only acted independently but, more interestingly, their effects were antagonistic, suggesting a role for these signals during T cell differentiation. The Ca2+ ionophore, ionomycin, increased the levels of intracellular free Ca2+ and induced the expression of the γ and δ chains of the T cell antigen receptor in a concentration‐dependent manner. The phorbol ester 12‐myristate 13‐acetate down‐regulated the basal γ TcR expression with marginal effect on δ TcR mRNA, but diminished the induction of both γ and δ TcR, initiated by the Ca2+ ionophore. These antagonistic effects of the two arms of the phospholipase C‐mediated signal transduction pathways, i.e. PKC activation and increased intracellular free Ca2+, were specific to the regulation of the γ and δ TcR, since the same signals exerted a synergistic effect on the mRNA levels of interleukin 2 receptor. These data confirm our hypothesis that the antagonistic regulation on the γ and δ TcR gene expression by phorbol esters and calcium ionophores occurs in the same cell, and stresses the biological significance of PKC activation and intracellular free calcium mobilization during intrathymic differentiation and selection. Copyright © 1991 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim