Expansion of CD56- NK cells in chronic HCV/HIV-1 co-infection: reversion by antiviral treatment with pegylated IFNalpha and ribavirin.
Co-infection with HCV and HIV-1 is a problem of increasing importance and the role of innate cellular immunity in this co-infection is incompletely understood. Here, we have observed sharply elevated numbers of CD56(-)CD16(+) perforin(low) NK cells in HCV/HIV-1 co-infected subjects on antiretroviral therapy. Interestingly, this expansion of unconventional CD56(-) NK cells rapidly reverted when HCV was suppressed by IFNalpha and ribavirin treatment, and was not seen in mono-infected control groups. In vitro experiments suggested that this effect of treatment was due to suppression of HCV viremia rather than a direct effect of IFNalpha on these cells. In contrast, the conventional CD56(+) NK cells were largely unchanged in subjects with high HCV loads, although they exhibited slightly decreased perforin expression. With delayed kinetics, the CD56(bright) immuno-regulatory NK cell subset temporarily increased to supranormal levels in response to HCV treatment. In contrast to the NK compartment, the CD1d-restricted NKT cells were severely reduced by the co-infection and not restored by treatment. Together, our data suggest that the high HCV loads in HCV/HIV-1 co-infection alter the NK cell compartment in a way not observed in HCV mono-infection.
Gonzalez
Veronica D
VD
Center for Infection Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden.
Falconer
Karolin
K
Michaëlsson
Jakob
J
Moll
Markus
M
Reichard
Olle
O
Alaeus
Annette
A
Sandberg
Johan K
JK
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D019002:CD56 Antigen / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D014766:Viremia / Q000188:drug therapy
D000998:Antiviral Agents; D019002:CD56 Antigen; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a