Suppressive effect of O,O-dimethyl, S-ethyl phosphorothioate on immune response

The effect of O,O-dimethyl, S-ethyl phosphorothioate (OO-Me S-Et) on macrophage function and the responses of T- and B-cells of the immune system were investigated using an in vitro model. The role of glutathione (GSH) enhancement of OO-Me S-Et suppression of immune responses was studied after either direct culturing with spleen or B-cells alone or coculture of B-cells with either B- or T-cells with or without preincubation with OO-Me S-Et and glutathione enriched cytosol. The results indicated that OO-Me S-Et, when preincubated with GSH, suppresses immune responses through an inhibition of B- and T-cell functions. Both cytotoxic T-lymphocyte (CTL) generation and antibody production were impaired. 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. It appears that the immunosuppressive effect of OO-Me S-Et is due to impairment of collaboration of T- and B-cells, i.e., mainly due to impairment of T-cell functions. The immunotoxic effect was only detectable when glutathione was present in the preincubation mixture.