Lymphocyte cytotoxicity to autologous hepatocytes in alpha1-antitrypsin deficiency

M. Mondelli, G. Mieli-Vergani, A. L W F Eddleston

Research output: Contribution to journalArticle

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Abstract

To investigate the possible role of cell mediated cytotoxicity in the pathogenesis or perpetuation of liver damage associated with alpha1-antitrypsin (AAT) deficiency, peripheral blood lymphocytes (PBL) from 13 children with PiZZ phenotype who had had liver disease in infancy were incubated with autologous hepatocytes in a microcytotoxicity assay. There was a clear trend for cytotoxicity to increase with age and thus significantly increased cytotoxicity was found in four cases older than 2 years, while intermediate values were recorded in three children between 6 months and 2 years and normal values in children younger than 6 months. Fractionation of PBL into T and non-T-enriched subsets showed that both were involved in the cytotoxic reaction. A purified liver membrane lipoprotein preparation (LSP) inhibited both T and non-T-cell cytotoxicity suggesting that LSP is a major target antigen in this system. Control experiments performed in infants with neonatal hepatitis syndrome, but with normal Pi phenotype, showed consistently increased cytotoxicity values. Cell-mediated immune reactions directed against autologous hepatocytes develop late in the course of the liver disease associated with AAT deficiency. While this reaction cannot be involved in the pathogenesis of the initial liver lesion, it may contribute to perpetuation of liver damage.

Original languageEnglish
Pages (from-to)1044-1049
Number of pages6
JournalGut
Volume25
Issue number10
Publication statusPublished - 1984

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Hepatocytes
Lymphocytes
Liver
Liver Diseases
Phenotype
Hepatitis
Lipoproteins
Reference Values
Antigens
Membranes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Mondelli, M., Mieli-Vergani, G., & Eddleston, A. L. W. F. (1984). Lymphocyte cytotoxicity to autologous hepatocytes in alpha1-antitrypsin deficiency. Gut, 25(10), 1044-1049.

Lymphocyte cytotoxicity to autologous hepatocytes in alpha1-antitrypsin deficiency. / Mondelli, M.; Mieli-Vergani, G.; Eddleston, A. L W F.

In: Gut, Vol. 25, No. 10, 1984, p. 1044-1049.

Research output: Contribution to journalArticle

Mondelli, M, Mieli-Vergani, G & Eddleston, ALWF 1984, 'Lymphocyte cytotoxicity to autologous hepatocytes in alpha1-antitrypsin deficiency', Gut, vol. 25, no. 10, pp. 1044-1049.
Mondelli, M. ; Mieli-Vergani, G. ; Eddleston, A. L W F. / Lymphocyte cytotoxicity to autologous hepatocytes in alpha1-antitrypsin deficiency. In: Gut. 1984 ; Vol. 25, No. 10. pp. 1044-1049.
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