Different mechanisms responsible for in vitro cell-mediated cytotoxicity to autologous hepatocytes in children with autoimmune and HbsAg-positive chronic liver disease

Mario Mondelli, Giorgina Mieli-Vergani, Flavia Bortolotti, Paolo Cadrobbi, Bernard Portmann, Alfredo Alberti, Giuseppe Realdi, Adrian L W F Eddleston, Alex P. Mowat

Research output: Contribution to journalArticle

Abstract

To investigate mechanisms of hepatocyte injury, lymphocytes from 41 children with chronic liver disease were incubated with autologous liver cells in a microcytotoxicity assay. Cytotoxicity was significantly increased in 18 of 25 patients with chronic hepatitis B virus (HBV) infection, in five of nine with "autoimmune" chronic active hepatitis (CAH), and in only one of seven with histologically inactive liver disorders. There was a good correlation between cytotoxicity and biochemical and histologic markers of disease activity in children with autoimmune CAH, whereas in HBsAg-positive disease a positive correlation was found only with serum alanine aminotransferase (SGPT). Children with autoimmune CAH receiving steroid treatment had normal cytotoxicity, whereas increased values were found in two of three HBsAg-positive patients receiving prednisolone. Fractionation studies revealed that non-T cells were cytotoxic in both autoimmune and HBsAg-positive chronic liver disease. T cell cytotoxicity was exclusively found in children with chronic HBV infection, particularly with HBe antigenemia. Blocking experiments showed that T-lymphocytes from HBsAg-positive children reacted with HBV core antigen on the hepatocyte surface. Non-T cells were directed against hepatocyte membrane antigens in both HBsAg-positive and HbsAg-negative children. These results suggest that different immune mechanisms of liver damage are involved in autoimmune and HBsAg-positive chronic liver disease.

Original languageEnglish
Pages (from-to)899-906
Number of pages8
JournalJournal of Pediatrics
Volume106
Issue number6
DOIs
Publication statusPublished - 1985

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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