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Cytotoxic CD4 + T cells in viral hepatitis
Author(s) -
Aslan N.,
Yurdaydin C.,
Wiegand J.,
Greten T.,
Ciner A.,
Meyer M. F.,
Heiken H.,
Kuhlmann B.,
Kaiser T.,
Bozkaya H.,
Tillmann H. L.,
Bozdayi A. M.,
Manns M. P.,
Wedemeyer H.
Publication year - 2006
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2006.00723.x
Subject(s) - perforin , cytotoxic t cell , cd8 , hepatitis b virus , immunology , virology , interleukin 21 , hepatitis b , hepatitis c virus , hepatitis , biology , medicine , immune system , virus , in vitro , biochemistry
Summary. CD4 + T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8 + T and B cells. However, perforin‐positive cytotoxic CD4 + T cells have been described in human immunodeficiency virus‐positive patients suggesting a role not only of CD8 + but also of CD4 + T cells for killing virus‐infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4 + T cells. The frequency of perforin‐positive CD4 + T cells in viral hepatitis was highly variable ranging from <1% to more than 25%. Perforin‐positive CD4 + T cells displayed the phenotype of terminally differentiated effector cells (CD28 − , CD27 − ). The highest frequencies of CD4 + cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis ( P = 0.04 vs HBV and HCV patients), and the presence of CD4 + CTLs was associated with elevated aspartate aminotransferase levels ( P = 0.01) and decreased platelet counts ( P = 0.03). Perforin‐positive CD4 + T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin‐expressing CD4 + cells and age ( P = 0.04), perforin‐positive CD8 + cells ( P < 0.001) and perforin‐positive CD4 − /CD8 − lymphoid cells ( P = 0.002). Differentiated CD27 − effector CD4 + CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin‐positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.