Suppressive and Enhancing Effect of T-2 Toxin on Murine Lymphocyte Activation and Interleukin 2 Production

Abstract

T-2 toxin, a fungal metabolite shown previously to exert potent immunosuppressive effects, was examined for its effects on activation and interleukin 2 (IL 2) production by murine and rat splenocytes. Splenocytes (1 × 10⁶ cells/well) were incubated with 1 μg Concanavalin A (Con A) for 48h at which time cellular protein and DNA synthesis by these cells were ascertained using radiolabeled precursors. IL 2 synthesis was determined from the cell supernatant using the IL 2-requiring cell line CTLL. Spleen cells from mice treated for 4 consecutive days with 2 mg/kg toxin exhibited a 50% reduction in in vitro Con A activation but the supernatant IL 2 levels from these cells was 4-fold higher than cells from control mice. In vitro exposure of Con A-activated normal spleen cells to various toxin doses for 48h resulted in diminished protein and DNA synthesis at 0.4 ng toxin with maximum inhibition at 1 ng (50% inhibition (TC1D₅₀) - 0.5 ng). Enhanced synthesis of both products was observed at lower toxin concentrations. IL 2 production by these cells followed a similar toxin dose response. Rat splenocytes were slightly more resistant and CTLL cells were slightly more sensitive to T-2 toxin than mouse splenocytes. These results indicate the variable effects a cytotoxic agent can have on lymphoid cells and that dosage is an important parameter for these effects.