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Biomedical subjects

Tina Deignan

Publications and source records attributed to Tina Deignan.

3 recordsLinked to original sources

Expansion of innate CD5pos B cells expressing high levels of CD81 in hepatitis C virus infected liver.

BACKGROUND/AIMS: Association of hepatitis C virus (HCV) with increased autoantibodies, mixed cryoglobulinaemia, non-Hodgkin's B-cell lymphoma and increased peripheral innate (CD5(pos)) B cells suggests a role for B-lymphocytes in the pathogenesis of HCV-infection. METHODS: Flow cytometry was used to estimate CD5(pos) B cell levels and CD81 co-expression in chronic HCV infection. Viral load was assessed using PCR. RESULTS: We demonstrate expansion of innate B cells in HCV-infected liver from patients with fibrosis score less than stage II (39%, % of total B cells, P=0.002) and end stage HCV cirrhosis (20%, P<0.05) compared with normal liver (8%). Expression of CD81, a signal transducing molecule and putative HCV receptor, was significantly increased on peripheral blood CD5(pos) B cells compared with conventional B cells (P=0.0001). Higher levels of CD81 on CD5(pos) B cells were more dramatic in the liver of HCV-infected individuals. However, no significant difference was observed in the viral load of CD5(pos)CD81(High) B cells and CD5(neg)CD81(Low) B cells. CONCLUSIONS: Increased expression of CD81 on innate B cells, a population that is expanded in the livers and peripheral blood of chronic HCV-infected patients, suggests a role in viral specific activation and clonal proliferation in chronic HCV infection.

Adult↗

Decrease in hepatic CD56(+) T cells and V alpha 24(+) natural killer T cells in chronic hepatitis C viral infection.

BACKGROUND/AIMS: The intrahepatic immune system is likely to play a key role in determining the outcome of hepatitis C virus (HCV) infection. The hepatic lymphocyte repertoire is characterised by high CD8/CD4 T cell ratios and large numbers of gamma delta T cells, natural killer (NK) cells, NK T cells and NK receptor-positive T cells. It is not known which of these populations contribute to immunity against HCV or immune pathology. METHODS: To explore the relative contributions of lymphocyte subpopulations, we have compared the intrahepatic lymphocyte repertoires and cytokine expression in 13 patients with mild chronic hepatitis C infection, 14 with end-stage hepatitis C cirrhosis and five histologically normal livers by flow cytometry and immunohistochemistry. RESULTS: CD4(+) T cells bearing alpha beta T cell receptors (TCR) were significantly expanded in livers with chronic HCV infection while CD56(+) alpha beta T cells and V alpha 24 TCR-positive T cells were significantly depleted. Expanded CD4(+)T cells were predominantly Th1 cells, producing interferon-gamma but not interleukin-4. CONCLUSIONS: Failure to resolve HCV infection may be due to deficient innate and/or memory immune responses, while Th1 cells may mediate immune pathology.

Adult↗

Localization of T and B lymphocytes in histologically normal adult human donor liver.

BACKGROUND/AIMS: Donor liver suitable for successful transplantation often has one or more of a range of mild abnormalities including inflammation. Passenger leukocytes documented in donor liver are thought to result from inflammatory stimuli in response to ischemic, drug or alcohol related damage. The aim was to identify donor livers, which were free of any evidence of damage, and to determine if, and where, leukocytes were present in these pristine livers. METHODOLOGY: Eight of eighteen donor livers, examined by hematoxylin and eosin staining, were found to be free of any evidence of pathological damage. Sections from these livers were stained with antibodies against CD3 (T cell marker), CD20 (B cell marker) and CD45 (common leukocyte antigen). RESULTS: Each of these livers were found to have significant numbers of T lymphocytes, located mainly in the portal tracts but also scattered throughout the parenchyma. A similar distribution of B cells was detected but at much lower levels. CONCLUSIONS: The presence of lymphocytes in the human liver is usually considered a hallmark of pathology. The demonstration of significant lymphocyte populations in pristine liver, particularly in the parenchyma, supports the hypothesis that the human liver harbors tissue-resident lymphocytes.

Adolescent↗