Carbon Tetrachloride Suppresses T-Cell-Dependent Immune Responses by Induction of Transforming Growth Factor-1
| Autor: | S C Strom, Bryan Delaney, S Collins, N E Kaminski |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
medicine.drug_class T-Lymphocytes T cell Mice Inbred Strains Spleen Biology Toxicology Monoclonal antibody digestive system Mice Immune system Transforming Growth Factor beta In vivo Internal medicine Immunopathology parasitic diseases medicine Animals Antibody-Producing Cells Receptor Carbon Tetrachloride Pharmacology Receptors Interleukin-2 digestive system diseases medicine.anatomical_structure Endocrinology Interleukin-2 Immunosuppressive Agents Transforming growth factor |
| Zdroj: | Toxicology and Applied Pharmacology. 126:98-107 |
| ISSN: | 0041-008X |
| DOI: | 10.1006/taap.1994.1095 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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