Immunosuppressive effect of an impurity of malathion: inhibition of murine T- and B-lymphocyte responses by O,O,S-trimethyl phosphorothioate.
The effect of O,O,S-trimethyl phosphorothioate (OOS-TMP) on immune responses such as antigen presentation, antibody production, and cytotoxic T-lymphocyte (CTL) function was examined in vitro. The roles of non-enzymatic and enzymatic glutathione (GSH) conjugation of OOS-TMP in these responses were studied. Antibody responses to T-dependent and T-independent antigens were evaluated after (i) direct culture with spleen or B cells; (ii) cocultivation of B cells with T cells with and without preincubation of OOS-TMP with GSH fortified cytosol. Antigen presentation by macrophages was also assessed after such treatment as compared to untreated controls. OOS-TMP preincubated with GSH had an inhibitory effect on the cytotoxic T lymphocyte and the direct hemolytic plaque forming cell responses. This was found to be mediated by a direct inhibitory effect on macrophages, T, and B cells of the immune system and not through the generation of regulatory suppressor T cells. Thus, the mode of suppressive action of OOS-TMP in vitro is due to inhibition of lymphocytic proliferation. This is only possible in the presence of glutathione which was determined to be a prerequisite for the induction of OOS-TMP suppressive effect.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D063086:Organothiophosphates / Q000494:pharmacology*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D012756:Sheep; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology
D008070:Lipopolysaccharides; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C048761:trinitrophenyl-lipopolysaccharide; C019123:O,O,S-trimethyl phosphorothioate