Acquired constitutive expression of interferon beta after gene transduction enhances human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity by a RANTES-dependent mechanism

CTL lines directed against HIV-1 antigens were generated from infected indi viduals and were transduced by the HMB-K(b)HuIFN beta vector, resulting in low, constitutive expression of interferon beta (IFN-beta), The IFN-beta-tr ansduced cells showed markedly increased HTV-1-specific, MHC class I-restri cted CTL activity against HIV-1-LAI Gag, Pol, or Env antigens, This effect of IFN-P was correlated with an overexpression of RANTES and completely abr ogated by RANTES-blocking antibody. The present results provide the first e vidence that IFN-beta transduction of CTL lines enhances HTV-specific cytot oxic activities through an upregulation of RANTES production. The efficient elimination of HIV-infected cells by IFN-beta-transduced CTL lines makes t his gene therapy approach an attractive treatment for AIDS.