Immunoprivileged status of the liver is controlled by Toll-like receptor 3 signaling

Karl S. Lang, Panco Georgiev, Mike Recher, Alexander A. Navarini, Andreas Bergthaler, Mathias Heikenwalder, Nicola L. Harris, Tobias Junt, Bernhard Odermatt, Pierre Alain Clavien, Hanspeter Pircher, Shizuo Akira, Hans Hengartner, Rolf M. Zinkernagel

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144 Citations (Scopus)


The liver is known to be a classical immunoprivileged site with a relatively high resistance against immune responses. Here we demonstrate that highly activated liver-specific effector CD8+ T cells alone were not sufficient to trigger immune destruction of the liver in mice. Only additional innate immune signals orchestrated by TLR3 provoked liver damage. While TLR3 activation did not directly alter liver-specific CD8+ T cell function, it induced IFN-α and TNF-α release. These cytokines generated expression of the chemokine CXCL9 in the liver, thereby enhancing CD8+ T cell infiltration and liver disease in mice. Thus, nonspecific activation of innate immunity can drastically enhance susceptibility to immune destruction of a solid organ.

Original languageEnglish
Pages (from-to)2456-2463
Number of pages8
JournalJournal of Clinical Investigation
Issue number9
Publication statusPublished - 1 Sep 2006
Externally publishedYes

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