Ethanol-altered liver-associated T cells mediate liver injury in rats administered Concanavalin A (Con A) or lipopolysaccharide (LPS).
BACKGROUND
Recent work from our laboratory implicates T cells in the pathogenesis of alcoholic liver disease. We have studied the role of liver-associated T cells in acute hepatitis produced in control rats administered Concanavalin A (Con A) after adoptive transfer of T cells from alcohol-consuming animals.


METHODS
Liver-associated T cells from ethanol-consuming rats were transferred via tail vein to nonethanol-consuming rats. They then received Con A (20 mg/kg body weight) intravenously. This produced a severe hepatitis. Serum was collected for the assay of alanine aminotransferase (ALT) and cytokines.


RESULTS
Hepatic necrosis was accompanied by an increase in plasma levels of ALT, interleukin-6, and tumor necrosis factor-alpha. These increases correlated with increased production of interleukin-6 and tumor necrosis factor-alpha in culture of liver-associated T cells stimulated or unstimulated with Con A. Immunohistology staining showed increased infiltration of inflammatory cells comprised of neutrophils and mononuclear cells, which included greater numbers of CD4+ T cells in the portal tract areas and around the central vein. Focal and lobular necrosis was seen with inflammatory cells in the necrotic area. Hepatocytes isolated from the liver showed increased apoptosis compared with rats that received liver-associated T cells from nonethanol-consuming rats. Injection of endotoxin LPS, in the same model, was associated with less hepatocyte injury indicating a distinct role for T cells as opposed to Kupffer cells in this model of liver disease.


CONCLUSIONS
Chronic ethanol consumption induces a lesion in a pool of liver-associated T cells which can mediate liver injury after polyclonal mitogen activation.
Cao
Q
Q
Department of Gastroenterology, John Hunter Hospital, Newcastle, New South Wales, Australia.
Batey
R
R
Pang
G
G
Clancy
R
R
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003208:Concanavalin A; D004731:Endotoxins; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006519:Hepatitis, Alcoholic / Q000209:etiology / Q000473:pathology*; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides; D008934:Mitogens; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
D002492:Central Nervous System Depressants; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D000431:Ethanol; D000410:Alanine Transaminase