Hepatitis resulting from liver-specific expression and recognition of self-antigen.
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(+) Valpha2 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.
Division of Gastroenterology, University of California, San Francisco, CA 94143, USA.
James
J
Buxbaum
Peiqing
P
Qian
Paul M
PM
Allen
Marion G
MG
Peters
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D019693:Hepatitis, Autoimmune / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D010047:Ovalbumin