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IFN‐γ‐producing γδT Cells Promote Liver Injury in Virus Infected Liver
Author(s) -
AJUEBOR MAUREEN,
Jin Y.,
Gremillion G.,
Chen Q.,
Adegboyega P.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1190.1
Subject(s) - cxcr3 , hepatocyte , liver injury , immune system , natural killer t cell , interferon , biology , immunology , t cell , hepatic stellate cell , chemokine , endocrinology , chemokine receptor , biochemistry , in vitro
γδT cells are a small population of CD3(+) innate immune T cells that are few in the liver (vs. the mucosal & brain), hence their role in viral liver infections is largely unknown. Adenovirus (AdV) was used to induce viral liver infection in male C57BL6 mice. Liver injury in response to AdV infection was paralleled by significant increases in the influx of γδT cells into the liver (by FACS) at days 1 and 6 (vs. control). Moreover, γδT cells were specifically localized in the hepatocytes. By FACS, we observed that AdV directly infect hepatic γδT cells to mediate increased IFN‐γ production by γδT cells. In addition, AdV infection mediated increased hepatic levels of IFN‐γ‐inducible/hepatocyte‐derived CXCR3 ligands. Both IFN‐γ KO and γδT cell KO mice were associated with significant reductions in (i) liver damage and (ii) hepatic levels of CXCR3 ligands (vs. WT mice) post‐AdV. Furthermore, CXCR3 Ab treatment significantly reduced liver‐infiltrating γδ T cells and hepatic injury post‐AdV. These results support our hypothesis that AdV directly infects/activates hepatic γ[delta]T cells to induce IFN‐γ production. IFN‐γ‐producing γ[delta]T cells subsequently act on hepatocytes in an autocrine manner to induce the production of hepatic CXCR3 ligands, which inturn exert liver damage by promoting/sustaining the influx of IFN‐γ‐producing γ[delta]T cells.