HGCL2-INDUCED INTERLEUKIN-4 GENE-EXPRESSION IN T-CELLS INVOLVES A PROTEIN-KINASE C-DEPENDENT CALCIUM INFLUX THROUGH L-TYPE CALCIUM CHANNELS

Mercuric chloride (HgCl2) induces T helper 2 (Th2) autoreactive anti-c lass II T cells in Brown Norway rats. These cells produce interleukin (IL)-4 and induce a B cell polyclonal activation that is responsible f or autoimmune disease. In Brown Norway rats, HgCl2 triggers early IL-4 mRNA expression both in vivo and in vitro by T cells, which may expla in why autoreactive anti-class II T cells acquire a Th2 phenotype. The aim of this study was to explore the transduction pathways by which t his chemical operates, By using two murine T cell hybridomas that expr ess IL-4 mRNA upon stimulation with HgCl2, we demonstrate that: 1) HgC l2 acts at the transcriptional level without requiring de novo protein synthesis; 2) HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels; 3) calcium/calcineurin-dependent path way and protein kinase C activation are both implicated in HgCl2-induc ed IL-4 gene expression; and 4) HgCl2 can activate directly protein ki nase C, which might be one of the main intracellular target for HgCl2. These data are in agreement with an effect of HgCl2 which is independ ent of antigen-specific recognition. It may explain the T cell polyclo naI activation in the mercury model and the expansion of pathogenic au toreactive anti-class II Th2 cells in this context.