Thiol levels in CD134-defined subsets of rat T lymphocytes: possible implications 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 costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation and 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 CD134+CD4+ cells than in CD134+CD4+ cells in both strains. In Lewis rats, total thiol levels in CD4+CD134+ cells, but not in CD4+CD134+ cells, were higher than in BN rats. In contrast, BN rats showed higher GSH levels in CD4+CD134+ cells, but not in CD4+CD134+ cells. In vitro exposure to HgCl2 decreased intracellular thiol levels, 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 CD134-defined subsets of CD4+ lymphocytes and subset-specific modification of thiol levels may contribute to differential lymphocyte activation by oxidizing chemicals.
Roos
A
A
Department of Pathology, University of Amsterdam, The Netherlands. j.roos@amc.uva.nl
Claessen
N
N
Schilder-Tol
E J
EJ
Chand
M A
MA
Weening
J J
JJ
Aten
J
J
D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism*; D008627:Mercuric Chloride / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013045:Species Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis* / Q000276:immunology
D015704:CD4 Antigens; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013438:Sulfhydryl Compounds; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D008627:Mercuric Chloride; D005978:Glutathione