THIOL LEVELS IN CD134-DEFINED SUBSETS OF RAT T-LYMPHOCYTES - POSSIBLEIMPLICATIONS FOR HGCL2-INDUCED IMMUNE DYSREGULATION

CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulat ion. Its expression is increased after exposure to the thiol-binding c ompound HgCl2 in BN rats, but not in Lewis rats, in association with i nduction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation a nd death in T lymphocytes. Therefore, we examined intracellular thiol levels in CD134-defined T cell subsets from BN and Lewis rats. Levels of total thiols and glutathione (GSH) were significantly higher in CD1 34(+)CD4(+) cells than in CD134(-)CD4(+) cells in both strains. In Lew is rats, total thiol levels in CD4(+)CD134(-) cells, but not in CD4(-) CD134(+) cells, were higher than in BN rats. In contrast, BN rats show ed higher GSH levels in CD4(+)CD134(+) cells, but not in CD4(+)CD134(- ) cells. In vitro exposure to HgCl2 decreased intracellular thiol leve ls, predominantly in CD4(+)CD134(-) cells. Furthermore, HgCl2-induced enrichment of CD134(+) viable cells was inversely correlated to HgCl2- induced cell death. Strain-dependent differences in thiol levels in CD 134-defined subsets of CD4(+) lymphocytes and subset-specific modifica tion of thiol levels may contribute to differential lymphocyte activat ion by oxidizing chemicals. (C) 1997 Academic Press.