Perforin expression in T cells and virological response to PEG-interferon alpha2b in HIV-1 infection.

OBJECTIVE AND
DESIGN: 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).
CONCLUSION: 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.