Elsevier

Hepatology

Volume 21, Issue 1, January 1995, Pages 190-198
Hepatology

Concanavalin A—induced T-cell—Mediated hepatic injury in mice: The role of tumor necrosis factor

https://doi.org/10.1016/0270-9139(95)90428-XGet rights and content

Abstract

Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of concanavalin A—induced liver injury. Here we report that hepatic injury is characterized by apoptotic cell death. On concanavalin A challenge, the cytokines tumor necrosis factor-α (TNFα), interleukin-2, granulocyte macrophage-colony stimulating factor, and interferon-γ were detectable in the circulation of the mice. Pretreatment of mice with anti-mouse TNF-α antiserum protected them from concanavalin A-induced liver injury. Nude mice failed to release TNF-α or interleukin-2 after concanavalin A challenge and were protected from liver injury. Lymph node cell transfer from responder mice to resistant nude mice resulted in susceptibility of the latter towards concanavalin A, i.e., to induction of cytokine release and hepatotoxicity. These experiments suggest that immunocompetent T cells play a pivotal role in concanavalin A—stimulated TNF-α release in vivo. After intravenous administration of fluorescein isothiocyanate-labeled concanavalin A to mice, the most fluorescence was found within the liver. In vitro, concanavalin A stimulation of separate cultures of mouse lymph node cells or nonparenchymal liver cells induced the release of minute amounts of TNF, whereas stimulation of cocultures of these cells resulted in production of substantial amounts of TNF-α. These findings may explain the hepatotropic effect of concanavalin A. In conclusion, T-cell-dependent concanavalin A-induced apoptotic liver injury in mice is related to immunological and cytokinemediated disorders and possibly to autoreactive hepatic processes.

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    Supported by the Deutsche Forschungsgemeinschft grant no. Ti 169/3.

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