CD3(+)CD56(+) Natural Killer-Like T Cells Display Anti-HCV Activity but Are Functionally Impaired in HIV(+) Patients With Acute Hepatitis C

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 70; no. 4; p. 338
• Main Authors: Kokordelis, Pavlos, Krämer, Benjamin, Boesecke, Christoph, Voigt, Esther, Ingiliz, Patrick, Glässner, Andreas, Wolter, Franziska, Srassburg, Christian P, Spengler, Ulrich, Rockstroh, Jürgen K, Nattermann, Jacob
• Format: Journal Article
• Language: English
• Published: United States 01.12.2015
• Subjects: Adult; CD3 Complex - analysis; CD56 Antigen - analysis; Cells, Cultured; Female; Flow Cytometry; Hepacivirus - immunology; Hepacivirus - physiology; Hepatitis C - immunology; Hepatocytes - virology; HIV Infections - complications; Humans; Interferon-gamma - secretion; Male; Middle Aged; Natural Killer T-Cells - chemistry; Natural Killer T-Cells - immunology; T-Lymphocyte Subsets - immunology; Virus Replication; Young Adult
• ISSN: 1944-7884
• DOI: 10.1097/QAI.0000000000000793

To analyze the role of CD3(+)CD56(+) natural killer (NK)-like T cells in HIV(+) patients with acute hepatitis C. Frequency, phenotype, and anti-hepatitis C virus (HCV) activity of CD3(+)CD56(+) NK-like T cells were studied in 36 HIV(+) patients with acute hepatitis C. As controls, 12 patients with chronic HCV/HIV coinfection, 8 HIV monoinfected patients, and 12 healthy donors were enrolled in this study. CD3(+)CD56(+) NK-like T-cell-mediated inhibition of HCV replication was analyzed using the HuH7A2HCVreplicon model. The CD3(+)CD56(+) NK-like T-cell phenotype and interferon (IFN)-γ secretion were studied by flow cytometry. Interleukin 12/interleukin 15 stimulated CD3(+)CD56(+) NK-like T cells from healthy donors effectively block HCV replication in vitro in an IFN-γ dependent manner. Accordingly, we found that blocking of IFN-γ with a specific antibody significantly reduced the antiviral activity of CD3(+)CD56(+) NK-like T cells. However, when CD3(+)CD56(+) NK-like T cells from HIV(+) patients were studied, we found HIV infection to be associated with a significantly impaired IFN-γ production, irrespective of HCV coinfection. Accordingly, CD3(+)CD56(+) NK-like T cells from HIV(+) patients were significantly less effective in blocking HCV replication in vitro than cells from healthy individuals. Taken together, our data indicate that HIV infection is associated with an impaired anti-HCV activity of CD3(+)CD56(+) NK-like T cells, which might represent a novel mechanism of dysregulated immune response in HIV/HCV-coinfected patients.