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Toll‐like receptor‐3 and the regulation of intrahepatic immunity: Implications for interferon‐alpha therapy
Author(s) -
Bertolino Patrick,
Holz Lauren E.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21504
Subject(s) - tlr3 , innate immune system , immune system , cd8 , immunology , chemokine , immunity , cxcr3 , cxcl9 , biology , t cell , toll like receptor , cytotoxic t cell , chemokine receptor , biochemistry , in vitro
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-alpha and TNF-alpha 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.