Essential Role of the Adhesion Receptor LFA-1 for T Cell-Dependent Fulminant Hepatitis
| Autor: | Mariko Iwamiya, Junichi Shindo, Goichi Matsumoto, Yasushi Ohmi, Daisuke Tone, Antonio J. Oliveira-dos-Santos, Josef M. Penninger, Keiichi Tsukinoki, Satoshi Tsunematsu |
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| Rok vydání: | 2002 |
| Předmět: |
Cytotoxicity
Immunologic Adoptive cell transfer Receptors Antigen T-Cell alpha-beta T cell Immunology chemical and pharmacologic phenomena Biology Lymphocyte Activation Cell Line Mice T-Lymphocyte Subsets Cell Adhesion Concanavalin A medicine Animals Immunology and Allergy Lectins C-Type Antigens Fulminant hepatitis Mice Knockout Hepatitis Liver cell Antibodies Monoclonal Proteins hemic and immune systems Intercellular Adhesion Molecule-1 medicine.disease Adoptive Transfer Molecular biology Lymphocyte Function-Associated Antigen-1 Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Liver Apoptosis Protein Biosynthesis Hepatocyte Antigens Surface Injections Intravenous Chemical and Drug Induced Liver Injury Viral hepatitis NK Cell Lectin-Like Receptor Subfamily B |
| Zdroj: | The Journal of Immunology. 169:7087-7096 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.12.7087 |
| Popis: | Viral hepatitis affects more than 2 billion people worldwide. In particular, no effective treatment exists to abrogate death and liver damage in fulminant hepatitis. Activation of T cells is an initial and critical event in the pathogenesis of liver damage in autoimmune and viral hepatitis. The precise molecular mechanisms that induce T cell-mediated hepatocyte injury remain largely unclear. In mice, T cell-dependent hepatitis and acute liver damage can be modeled using ConA. In this study, we examined the role of the adhesion receptor LFA-1 in ConA-induced acute hepatic damage using LFA-1−/− (CD11a) mice. Massive liver cell apoptosis and metabolic liver damage were observed in LFA-1+/+ mice following ConA injection. By contrast, LFA-1−/− mice were completely resistant to ConA-induced hepatitis and none of the LFA-1−/− mice showed any hepatic damage. Whereas activated hepatic T cells remained in the liver in LFA-1+/+ mice, activated T cells were rapidly cleared from the livers of LFA-1−/− mice. Mechanistically, T cells from LFA-1−/− mice showed markedly reduced cytotoxicity toward liver cells as a result of impaired, activation-dependent adhesion. Importantly, adoptive transfer of hepatic T cells from LFA-1+/+ mice, but not from LFA-1−/− mice, sensitized LFA-1−/− mice to ConA-induced hepatitis. Thus, LFA-1 expression on T cells is necessary and sufficient for T cell-mediated liver damage in vivo. These results provide the first genetic evidence on an adhesion receptor, LFA-1, that has a crucial role in fulminant hepatitis. These genetic data identify LFA-1 as a potential key target for the treatment of T cell-mediated hepatitis and the prevention of liver damage. |
| Databáze: | OpenAIRE |
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