Suppressive and enhancing effect of T-2 toxin on murine lymphocyte activation and interleukin 2 production.
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 X 10(6) cells/well) were incubated with 1 microgram Concanavalin A (Con A) for 48 h 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 48 h resulted in diminished protein and DNA synthesis at 0.4 ng toxin with maximum inhibition at 1 ng (50% inhibition (TCID50) = 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.
Holt
P S
PS
U.S. Department of Agriculture, Veterinary Toxicology and Entomology Research Laboratory, College Station, Texas 77841.
Corrier
D E
DE
DeLoach
J R
JR
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D012717:Sesquiterpenes / Q000494:pharmacology*; D013605:T-2 Toxin / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D012717:Sesquiterpenes; D013605:T-2 Toxin