CARBON-TETRACHLORIDE SUPPRESSES T-CELL-DEPENDENT IMMUNE-RESPONSES BY INDUCTION OF TRANSFORMING GROWTH-FACTOR-BETA-1

In vivo exposure of B6C3F1 mice to the hepatotoxic chlorinated hydroca rbon, CCl4, suppresses T-cell-dependent humoral immune responses to sR BC. In the present studies, separation-crossover-reconstitution experi ments with spleen cell subpopulations isolated from vehicle and CCl4-t reated mice (500 mg/kg/day for 7 days) indicate that T-cells are the p rimary immunologic cell-type altered following CCl4 exposure. Despite suppression of T-cell activity, Con A-activated spleen cell supernatan ts from CCl4-treated mice produced greater amounts of biologically act ive IL-2 than untreated spleen cells. Furthermore, Con A-induced upreg ulation of the p55 subunit of the IL-2 receptor was not altered in spl een cells from CCl4-treated mice. The mediator of immune suppression i s a serum-borne factor induced 48 hr following a single exposure to CC l4. Sera isolated from mice treated with CCl4 for 7 days (500 mg/kg/da y) or 48 hr following a single exposure (1000 mg/kg) were found to pos sess high concentrations of TGF-beta 1. Direct addition studies demons trated that T-cell-dependent AFC responses are more sensitive to suppr ession by TGF-beta 1 than are T-cell-independent responses. Finally, i ncubation of sera from CCl4-treated mice with TGF-beta 1-neutralizing mAb reversed the immune suppression associated with this serum. These results demonstrate that CCl4-induced immune suppression is at least p artially mediated by induction of TGF-beta 1. (C) 1994 Academic Press, Inc.