Perforin expression in T cells and virological response to PEG-interferon alpha2b in HIV-1 infection.
OBJECTIVE
Interferon alpha (IFNalpha), which is known to directly inhibit the HIV-1 replicative cycle and to increase the activity of cytotoxic T lymphocytes (CTL), is being tested as an anti-HIV agent. As CTL play a major role in immune defence against HIV, we wanted to further characterize CTL activity and the effect of IFNalpha on it.


METHODS
We followed by flow cytometry the intracellular expression of the key mediator of cytotoxicity, perforin, in peripheral blood T cells of patients treated with IFNalpha.


RESULTS
We observed that the percentage of T cells harbouring perforin was higher in infected subjects than in non-infected controls. Administration of IFNalpha2b attached to polyethylene glycol increased this perforin expression further and reduced viral load (P = 0.010). The increase in the percentage of T cells expressing perforin correlated with IFNalpha-induced decrease in viral load (r, 0.753; P = 0.003). In addition, the level of perforin expression before IFNalpha administration was inversely correlated with viral load remaining after IFNalpha administration (r, -0.647; P= 0.017).


CONCLUSIONS
The pre-therapeutic percentage of perforin-positive T cells might be a predictive marker of the virological response to IFNalpha in HIV-1-infected patients.
Portales
Pierre
P
Laboratoire d'Immunologie, Hôpital Saint Eloi, Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, Montpellier, France.
Reynes
Jacques
J
Rouzier-Panis
Régine
R
Baillat
Vincent
V
Clot
Jacques
J
Corbeau
Pierre
P
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D054353:Perforin; D011092:Polyethylene Glycols / Q000627:therapeutic use; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D054353:Perforin; D011092:Polyethylene Glycols