Erhardt AL, Biburger M, Papadopoulos T, Tiegs G (2007)
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2007
Publisher: Wiley-Blackwell
Book Volume: 45
Pages Range: 475-485
Journal Issue: 2
DOI: 10.1002/hep.21498
The liver appears to play an important role in immunological tolerance, for example, during allo-transplantation. We investigated tolerance mechanisms in the model of concanavalin A (ConA)-induced immune-mediated liver injury in mice. We found that a single injection of a sublethal ConA dose to C57BL/6 mice induced tolerance toward ConA-induced liver damage within 8 days. This tolerogenic state was characterized by suppression of the typical Th1 response in this model and increased IL-10 production. Tolerance induction was fully reversible in IL-10 mice and after blockade of IL-10 responses by anti-IL10R antibody. Co-cultures of CD4CD25 regulatory T cells (Ts) and CD4CD25 responder cells revealed T from ConA-tolerant mice being more effective in suppressing polyclonal T cell responses than T from control mice. Moreover, T from tolerant but not from control mice were able to augment in vitro IL-10 expression. Depletion by anti-CD25 monoclonal antibody (MAb) indicated a functional role of Ts in ConA tolerance in vivo. Cell depletion studies revealed Ts and Kupffer cells (KC) to be crucial for IL-10 expression in ConA tolerance. Studies with CD1d mice lacking natural killer T (NKT) cells disclosed these cells as irrelevant for the tolerogenic effect. Finally, cellular immune therapy with CD4 CD25 cells prevented ConA-induced liver injury, with higher protection by T from ConA-tolerized mice. Conclusion: The immunosuppressive cytokine IL-10 is crucial for tolerance induction in ConA hepatitis and is mainly expressed by CD4CD25 T and KC. Moreover, Ts exhibit therapeutic potential against immune-mediated liver injury. Copyright © 2007 by the American Association for the Study of Liver Diseases.
APA:
Erhardt, A.L., Biburger, M., Papadopoulos, T., & Tiegs, G. (2007). IL-10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice. Hepatology, 45(2), 475-485. https://doi.org/10.1002/hep.21498
MLA:
Erhardt, Annette Lydia, et al. "IL-10, regulatory T cells, and Kupffer cells mediate tolerance in concanavalin A-induced liver injury in mice." Hepatology 45.2 (2007): 475-485.
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