CD3(+)CD56(+) Natural Killer-Like T Cells Display Anti-HCV Activity but Are Functionally Impaired in HIV(+) Patients With Acute Hepatitis C.
OBJECTIVE
To analyze the role of CD3(+)CD56(+) natural killer (NK)-like T cells in HIV(+) patients with acute hepatitis C.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
*Department of Internal Medicine I, University of Bonn, Bonn, Germany; †German Center for Infection Research (DZIF), Bonn, Germany; ‡Praxis am Ebertplatz, Cologne, Germany; and §Medical Center for Infectious Diseases (MID), Berlin, Germany.
Pavlos
P
Kokordelis
Benjamin
B
Krämer
Christoph
C
Boesecke
Esther
E
Voigt
Patrick
P
Ingiliz
Andreas
A
Glässner
Franziska
F
Wolter
Christian P
CP
Srassburg
Ulrich
U
Spengler
Jürgen K
JK
Rockstroh
Jacob
J
Nattermann
D000328:Adult; D017252:CD3 Complex / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000737:chemistry / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014779:Virus Replication; D055815:Young Adult
D017252:CD3 Complex; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D007371:Interferon-gamma