Modulation of cellular and humoral immune responses by O,S,S-trimethyl phosphorodithioate, an impurity of commercial malathion.
We studied the effect of O,S,S-trimethyl phosphorodithioate (OSS-Me) on macrophage function and the immune responses of both T- and B-cells using an in vitro system. The involvement of glutathione (GSH) in the bioactivation of OSS-Me to suppress such responses was investigated after either direct culture with spleen or B-cells and/or co-culture of B-cells with either B- or T-cells that were or were not preincubated with OSS-Me and glutathione enriched cytosol. Our results show that OSS-Me preincubated with GSH suppresses immune responses through an inhibitory effect on the cell function. Both cytotoxic T-lymphocyte (CTL) generation and antibody production were impaired. Antigen presentation by macrophages was also inhibited. In mixing experiments of pretreated and normal cells, the inhibitory effect was also observed on macrophages and helper T-cells responding to a T-dependent antigen. We concluded that the immunosuppressive effect of OSS-Me is due to impairment of cell function and not mediated through generation of regulatory suppressor T-cells. This inhibitory effect was only detectable in the presence of glutathione in the preincubation mixture, suggesting that an OSS-Me glutathione adduct might be responsible for the toxic effect.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005978:Glutathione / Q000276:immunology / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D063086:Organothiophosphates / Q000276:immunology* / Q000494:pharmacology; D009946:Organothiophosphorus Compounds / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; C033125:O,S,S-trimethyl phosphorodithioate; D005978:Glutathione