Interferon-alpha restores HIV-induced alteration of natural killer cell perforin expression in vivo.
OBJECTIVE
The percentage and the activity of natural killer (NK) cells are known to be decreased in HIV-infected patients. However, the mechanisms responsible for this NK deficiency are poorly understood. Because of the role of NK cells in the host defence against microbial infections, this defect contributes to the virus-induced immune deficiency. The aim of the present study was to better understand this defect in order to be able to restore NK function in HIV infection.


METHODS
The expression of the cytolytic mediators perforin and granzyme A was analysed by flow cytometry, the lytic activity of peripheral blood NK cells of HIV-infected patients was analysed by cytotoxic assay, and the expression of perforin was followed during administration of interferon (IFN)alpha attached to polyethylene glycol (PEG)-IFNalpha.


RESULTS
The lytic activity and the expression of perforin and granzyme A was low in NK cells of infected individuals in comparison with normal control volunteers. In both groups NK cytotoxic capacity was linked to perforin expression. The low perforin expression in HIV-infected subjects negatively correlated with HIV RNA plasma level. administration of PEG-IFNalpha restored perforin expression even in patients whose viral load was not reduced by this treatment.


CONCLUSIONS
These results suggest that HIV-induced NK deficiency could be partly mediated by a defect in perforin and granzyme A expression, and that PEG-IFNalpha could be used in infected subjects to directly improve their natural immunity in addition to eventually reducing their viraemia.
Portales
Pierre
P
Laboratoire d'Immunologie, Hôpital Saint Eloi, the Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, Montpellier, France.
Reynes
Jacques
J
Pinet
Valérie
V
Rouzier-Panis
Régine
R
Baillat
Vincent
V
Clot
Jacques
J
Corbeau
Pierre
P
D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D053804:Granzymes; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007424:Intracellular Fluid / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D014766:Viremia
D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human