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1.
Eur J Gastroenterol Hepatol ; 9(5): 491-6, 1997 May.
Article in English | MEDLINE | ID: mdl-9187883

ABSTRACT

OBJECTIVE: Beside the hypothesis of a direct viral cytopathy, several lines of evidence argue in favour of hepatic damage triggered by immune-mediated mechanisms in hepatitis C virus (HCV) infection. The intrahepatic localization of HCV antigen-specific cytotoxic T-lymphocytes (CTLs) to disease sites has been described; however, very few data are available about the degree and the role of hepatic-infiltrating natural killer (NK) cells in chronically HCV-infected subjects. DESIGN: In a series of percutaneous needle liver biopsies obtained from 35 consecutive untreated patients with chronic active hepatitis C, we performed an in-situ immunophenotyping study to evaluate the degree of cytotoxic NK cell infiltration as compared to CTLs, the hepatocyte expression of human major histocompatibility complex antigens class I and class II (HLA-I and HLA-II), and cell adhesion molecules (CAM) in the context of liver inflammatory infiltrates. The data were correlated with the histological activity index (HAI) of disease. RESULTS: In-situ immunophenotyping analysis of CAM provided evidence for the intrahepatic expression of leucocyte adhesion molecules (CD11a and CD2) and their corresponding ligands on hepatocytes (CD54 and CD58) in all cases. A significant parallel expression of CD11a and CD54 as well as CD2 and CD58 structures, restricted to hepatic lobules within the disease sites, was also observed, even if their induction exhibited different degrees of correlation with biological and/or histological activities. A membranous pattern of HLA-I and HLA-II antigen expression on hepatocyte clusters was found in all tissue samples, although HLA-I expression was significantly higher than HLA-II. Moreover, lymphocyte subset analysis displayed a CD8+ T-cell lobular infiltration within inflammatory and/or spotty necrosis areas in all cases, while CD4+ T-cells were confined to the portal and periportal levels. A few scattered CD56+ and CD16+ NK cells, mainly distributed at periportal areas within inflammatory and/or necrotic foci, were detected in 7/35 (20%) and in 5/35 (14.2%) cases, respectively. On the other hand, CD8+ T-cell lobular expression exhibited a linear correlation with HAI (r: 0.698, P < 0.01). Finally, cytotoxic cell infiltration degree did not correlate with HCV serotypes. CONCLUSION: Our findings suggest a limited role for NK cells in the immune mechanism of liver injury in chronic active hepatitis C, while providing further support for the involvement of CD8+ T-cells at disease sites.


Subject(s)
Hepatitis C/immunology , Hepatitis, Chronic/immunology , Immunophenotyping/methods , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/immunology , Adult , Aged , Analysis of Variance , Biopsy, Needle , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Adhesion Molecules/metabolism , Cytotoxicity, Immunologic , Female , Hepacivirus/immunology , Hepatitis C/pathology , Hepatitis C Antibodies/analysis , Hepatitis, Chronic/pathology , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Killer Cells, Natural/immunology , Male , Middle Aged
2.
Microbios ; 92(371): 73-82, 1997.
Article in English | MEDLINE | ID: mdl-9589606

ABSTRACT

A liver tissue recruitment of antigen-specific cytotoxic cells has been reported in chronic hepatitis C virus (HCV) infection, but whether they really play a role in viral clearance is still a matter of investigation. To further evaluate T-cell involvement in HCV-induced hepatic disease, the authors analysed, in a cohort of chronic hepatitis C patients, the intrahepatic T-cell expression of CD45 isoforms by using specific monoclonal antibodies. Within hepatic specimens, CD45RA+ (naive) cell frequency at the portal tract level was significantly higher than that exhibited at lobular level. At the same time, a large number of CD45RO+ (memory) cells was found at periportal sites in comparison with the lobular counterpart. The evaluation of CD45RA and CD45RO isoform topographical distribution in relation to CD4+ and CD8+ lymphocytes, as determined on serial sections, showed that CD45RA antigen expression was predominantly coexpressed with CD4+ lymphocytes at the portal tract level, and the CD45RO phenotype with CD8 structure at the lobular and periportal sites. The levels of CD45 isoforms did not show any correlation with biological and/or histological disease activities. The results suggest that a liver recruitment of both naive and memory cells occurs during chronic HCV infection, even if their functional role needs to be further clarified.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Gene Expression Regulation, Viral/genetics , Hepacivirus/genetics , Hepatitis C, Chronic/genetics , Leukocyte Common Antigens/genetics , Liver/immunology , Adolescent , Adult , Aged , Animals , Antibodies, Monoclonal/immunology , Biopsy, Needle , Cohort Studies , Female , Gene Expression Regulation, Viral/immunology , Hepacivirus/immunology , Hepatitis C, Chronic/immunology , Humans , Image Interpretation, Computer-Assisted , Immunohistochemistry , Leukocyte Common Antigens/chemistry , Leukocyte Common Antigens/immunology , Liver/cytology , Male , Mice , Middle Aged , Rabbits
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