Carbon tetrachloride suppresses T-cell-dependent immune responses by induction of transforming growth factor-beta 1

Delaney, B; Strom, SC; Collins, S; Kaminski, NE

HERO ID

194748

Reference Type

Journal Article

Year

1994

Language

English

PMID

8184439

HERO ID 194748
In Press No
Year 1994
Title Carbon tetrachloride suppresses T-cell-dependent immune responses by induction of transforming growth factor-beta 1
Authors Delaney, B; Strom, SC; Collins, S; Kaminski, NE
Journal Toxicology and Applied Pharmacology
Volume 126
Issue 1
Page Numbers 98-107
Abstract In vivo exposure of B6C3F1 mice to the hepatotoxic chlorinated hydrocarbon, CCl4, suppresses T-cell-dependent humoral immune responses to sRBC. In the present studies, separation-crossover-reconstitution experiments with spleen cell subpopulations isolated from vehicle and CCl4-treated mice (500 mg/kg/day for 7 days) indicate that T-cells are the primary immunologic cell-type altered following CCl4 exposure. Despite suppression of T-cell activity, Con A-activated spleen cell supernatants from CCl4-treated mice produced greater amounts of biologically active IL-2 than untreated spleen cells. Furthermore, Con A-induced upregulation of the p55 subunit of the IL-2 receptor was not altered in spleen cells from CCl4-treated mice. The mediator of immune suppression is a serum-borne factor induced 48 hr following a single exposure to CCl4. Sera isolated from mice treated with CCl4 for 7 days (500 mg/kg/day) or 48 hr following a single exposure (1000 mg/kg) were found to possess high concentrations of TGF-beta 1. Direct addition studies demonstrated that T-cell-dependent AFC responses are more sensitive to suppression by TGF-beta 1 than are T-cell-independent responses. Finally, incubation 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 partially mediated by induction of TGF-beta 1.
Doi 10.1006/taap.1994.1095
Pmid 8184439
Wosid WOS:A1994NL85400013
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Is Qa No