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 individuals and were transduced by the HMB-KbHuIFNbeta vector, resulting in low, constitutive expression of interferon beta (IFN-beta). The IFN-beta-transduced cells showed markedly increased HIV-1-specific, MHC class I-restricted CTL activity against HIV-1-LAI Gag, Pol, or Env antigens. This effect of IFN-beta was correlated with an overexpression of RANTES and completely abrogated by RANTES-blocking antibody. The present results provide the first evidence that IFN-beta transduction of CTL lines enhances HIV-specific cytotoxic activities through an upregulation of RANTES production. The efficient elimination of HIV-infected cells by IFN-beta-transduced CTL lines makes this gene therapy approach an attractive treatment for AIDS.