MERCURIC-CHLORIDE, A CHEMICAL RESPONSIBLE FOR T-HELPER CELL (TH)2-MEDIATED AUTOIMMUNITY IN BROWN-NORWAY RATS, DIRECTLY TRIGGERS T-CELLS TO PRODUCE IN INTERLEUKIN-4

Mercurials may induce immune manifestations in susceptible individuals . Mercuric chloride (HgCl2) induces autoimmunity in the Brown Norway ( BN) strain but an immunesuppression in the Lewis strain with, however, autoreactive anti-class II T cells present int both strains. In the p resent study we looked at modifications of cytokine production by PCR and cytofluorometric analyses in normal BN and Lewis rat splenocytes, cultured with or without HgCl2. Unfractionated BN rat splenocytes and purified T cells exposed to HgCl2 expressed high levels of IL-4 mRNA. Increase in class II and CD23 molecule expression on B cells was partl y inhibited by anti-IL-4 mAb showing that IL-4 was produced, By contra st, no overexpression of IL-4 mRNA could be seen in Lewis rats. Althou gh an increase in class II molecule expression was observed suggesting that other T helper cell 2 cytokines were produced, there was also a concomitant decrease in CD23 molecule expression that was abrogated af ter addition of an anti-IFN-gamma mAb to the culture. IFN-gamma mRNA p roduction was induced in unfractionated spleen cells and T cells from both strains after HgCl2 exposure. Altogether these findings demonstra te that HgCl2 has very early direct effects on cytokine production and that these effects differ depending on the strain, The early effect o n IL-4 production observed on BN rat spleen cells and T cells may expl ain that the autoreactive anti-class II T cells that are found in HgCl 2-injected BN rats have a Th2 phenotype.