Cyclosporin A Blocks PMA and Ionomycin Activated Lymphotoxin Expression in a Human T-Cell Line

LTalpha and LTbeta represent subunits of lymphotoxin complexes, forming either a soluble homotrimeric complex (LTalpha(3)), which binds to and signals through CD120a/b (TNFRp55 and p75), or a membrane-associated heterotrimeric complex (LTalpha(1)beta(2)), which binds to and signals through the LTbeta receptor (LTbetaR). While it was demonstrated that the LTalpha(1)beta(2) complex is essential for organogenesis and the functional organization of secondary lymphoid organs, regulation of the biosynthesis of the LT components is not fully understood. We studied regulation of LTalpha and LTbeta gene expression in human T-cell line MOLT4, with special emphasis on the modulatory effects of the immunosuppressant cyclosporin A (CsA). CsA downregulates PMA/ionomycin-induced LTalpha at both transcription and protein expression levels, whereas it downregulates LTbeta at the transcript but not at the protein expression levels. Our data suggest that intracellular calcium homeostasis determines the balance of LTalpha and LTbeta in human T cells.