Immunosuppression in vitro by a metabolite of a human pathogenic fungus.

Gliotoxin , a metabolite of Aspergillus fumigatus, inhibits phagocytosis of macrophages at concentrations of 20-50 ng/ml. Pretreatment of stimulator cells in mixed lymphocyte cultures with gliotoxin (100 ng/ml) abrogates induction of alloreactive cytotoxic T cells. The presence of gliotoxin 48 hr after initiation of cytotoxic T-cell induction has no effect. Inhibition of cytotoxic T-cell induction by gliotoxin at low concentrations, acting on the stimulator cells, can be overridden by concanavalin A-activated cell supernatants. Gliotoxin does not induce immediate cell-surface antigen modification on target cells. The possible role of gliotoxin in the etiology of A. fumigatus-related diseases is discussed.