title: Monitoring intrahepatic CD8+ T cells by fine-needle aspiration cytology in chronic hepatitis C infection.
abstract: Infection of the liver with hepatitis C virus (HCV) causes compartmentalization of CD8+ cytotoxic T cells to the site of disease. These cells are thought to be involved in viral clearance during interferon therapy. The repetitive analysis of the intrahepatic immune response is hampered by the difficulty to obtain the intrahepatic T cells. The fine-needle aspiration biopsy (FNAB) technique was evaluated for its use to obtain liver-derived CD8+ T cells in a minimally invasive way. In 26 chronic HCV patients who were evaluated for Peg-interferon and ribavirin combination therapy, pre-treatment FNABs and peripheral blood specimens were obtained simultaneously with liver tissue biopsies, and CD3+ and CD8+ T cells were quantified by immunocytochemistry. The CD8+/CD3+ ratio was significantly higher in the FNABs than in peripheral blood (P < 0.01), and similar to those in portal areas in the tissue biopsies. A significant correlation was observed between numbers of CD3+CD8+ T lymphocytes in the FNABs and the numbers of CD8+ cells in the lobular fields or in the portal tracts of the liver tissue biopsies, but not with CD3+CD8+ T lymphocytes in peripheral blood. Finally, the ratio of CD8+/CD3+ T lymphocytes in FNABs was significantly higher in those patients who responded rapidly to therapy when compared with slow responders at 4 weeks of treatment (P = 0.02). These findings demonstrate that the intrahepatic T-cell composition is reflected in FNABs, and that the FNAB technique can be used for predicting early virological response to therapy of patients chronically infected with HCV.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Vrolijk
authors.forename: T J
authors.initials: TJ
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: B L
authors.initials: BL
authors.lastname: Haagmans
authors.forename: A J
authors.initials: AJ
authors.lastname: Herscheid
authors.forename: J G
authors.initials: JG
authors.lastname: Kusters
authors.forename: H L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: J T
authors.initials: JT
authors.lastname: Brouwer
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
mesh_terms: D044963:Biopsy, Fine-Needle; D001773:Blood Cells / Q000187:drug effects; D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002452:Cell Count; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000473:pathology*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D017252:CD3 Complex; D016827:CD8 Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a