MODULATION OF ENDOPLASMIC-RETICULUM CALCIUM-PUMP EXPRESSION DURING T-LYMPHOCYTE ACTIVATION

Calcium mobilization from intracellular storage organelles is a key co mponent of the second messenger system inducing cell activation. Calci um transport ATPases associated with intracellular calcium storage org anelles play a major role in controlling this process by accumulating calcium from the cytosol into intracellular calcium pools. In this stu dy the modulation of the expression of the sarco-endoplasmic reticulum calcium transport ATPase (SERCA) isoenzymes has been studied in lymph ocytes undergoing phorbol myristate acetate and ionomycin-induced acti vation. In several T lymphocyte cell lines a combined treatment by the two drugs resulted in an approximately 90% decrease of the expression of the calcium pump isoform recognized by the PLIM430 isoform-specifi c antibody, whereas the expression of the SERCA 2b isoform was increas ed approximately 2-fold. Phorbol ester or ionomycin applied separately was ineffective, In Jurkat T cells the downmodulation of expression o f the SERCA isoform recognized by the PLIM430 antibody appeared concom itantly with the induction of interleukin-2 expression and could be in hibited by the immunosuppressant drug cyclosporine-A. These data indic ate that T cell activation induces a selective and cyclosporine-A-sens itive modulation of the expression of the SERCA calcium pump isoforms, This reflects a profound reorganization of the calcium homeostasis of T cells undergoing activation and may open new avenues in the underst anding of the plasticity of the calcium homeostasis of differentiating cells and in the pharmacological modulation of lymphocyte function.