Interferon β Transduction of Peripheral Blood Lymphocytes from HIV-Infected Donors Increases Th1-Type Cytokine Production and Improves the Proliferative Response to Recall Antigens

We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) β . Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-HbHuIFNβ retroviral vector. The constitutive low production of IFN-β in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4+cells, and this protective effect was observed only in the PBL derived from donors having a CD4+cell count above 200 per mm3. In IFN-β -transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-γ and interleukin (IL)-12 was enhanced. In IFN-β -transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor α was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL. The proliferative response to recall antigens was partially restored in IFN-β -transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-β transduction of PBL from HIV-infected donors improves several parameters of immune function.