Hepatitis resulting from liver-specific expression and recognition of self-antigen

James Buxbaum, Peiqing Qian, Paul M. Allen, Marion G. Peters

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Liver-specific immune reactivity in response to aberrant expression of antigen on the surface of hepatocytes is thought to be a major factor in development of autoimmune hepatitis (AIH). Persistent inflammation develops when these antigens are not eliminated and/or responses are not appropriately regulated. We have developed transgenic mice (OVA-HEP), which express chicken ovalbumin on the surface of hepatocytes. These mice are tolerant to ovalbumin, develop normally and have shown no evidence of liver or other disease up to 2 years of age. Adoptive transfer of naïve ovalbumin-specific T cells into OVA-HEP transgenic mice led to liver-specific inflammation in a dose dependent manner. This hepatic necroinflammation was dependent upon CD8+ Vα2 OVA-specific T cells, was limited to the liver, and was augmented by OVA-specific CD4+ T cell help; but did not result from adoptive transfer of ovalbumin-specific CD4 T cells alone. The response was self-limited but persistent inflammation developed after repeated transfer of antigen-specific T cells. This model of T cell recognition of antigen on hepatocytes may be used to understand many liver-specific aspects of the immune response in autoimmune hepatitis.

Original languageEnglish
Pages (from-to)208-215
Number of pages8
JournalJournal of Autoimmunity
Volume31
Issue number3
DOIs
StatePublished - Nov 2008

Keywords

  • Acute hepatitis
  • Antigen-specific
  • Autoimmune hepatitis (AIH)
  • Autoimmunity
  • Chronic hepatitis

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