Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A.
The pathogenic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T-cell clones from liver biopsies from four patients with hepatitis A. A total of 578 clones was phenotypically analysed. During the acute phase of the disease CD8+ clones dominated over CD4+ clones, whereas in a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- 'NK-like' phenotype. All CD8+ clones had cytotoxic activity and approximately 50% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus. The CD8+ cells also produced IFN-gamma in response to these target cells. Variable IFN-gamma production was observed with all types of T-cell clones. These results suggest that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8-T-cell receptor alpha beta-chain-negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an anti-viral reaction.
Fleischer
B
B
Department of Medical Microbiology and Immunology, University of Ulm, FRG.
Fleischer
S
S
Maier
K
K
Wiedmann
K H
KH
Sacher
M
M
Thaler
H
H
Vallbracht
A
A
D000208:Acute Disease; D000954:Antigens, Surface / Q000032:analysis; D015152:Blotting, Northern; D002648:Child; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006506:Hepatitis A / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell