title: Cytotoxic CD4 T cells in viral hepatitis.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Aslan
authors.forename: C
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: J
authors.initials: J
authors.lastname: Wiegand
authors.forename: T
authors.initials: T
authors.lastname: Greten
authors.forename: A
authors.initials: A
authors.lastname: Ciner
authors.forename: M F
authors.initials: MF
authors.lastname: Meyer
authors.forename: H
authors.initials: H
authors.lastname: Heiken
authors.forename: B
authors.initials: B
authors.lastname: Kuhlmann
authors.forename: T
authors.initials: T
authors.lastname: Kaiser
authors.forename: H
authors.initials: H
authors.lastname: Bozkaya
authors.forename: H L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: A M
authors.initials: AM
authors.lastname: Bozdayi
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000821:virology; D006508:Hepatitis Antibodies / Q000097:blood; D006518:Hepatitis Viruses / Q000276:immunology*; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
chemical_list: D015483:HIV Antibodies; D006508:Hepatitis Antibodies; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin