Genetic Vaccination-Induced Immune Responses to the Human Immunodeficiency Virus Protein Rev: Emergence of the Interleukin 2-Producing Helper T Lymphocyte

Abstract

Overview summary The immune system poses a major obstacle to the long-term success of in vivo gene therapies. Immune responses to foreign transgene products and/or the vectors that facilitate gene transfer may neutralize the transgene product, eliminate transfected cells, and culminate in inflammation within transfected tissues. The majority of studies that address these issues have focused on cytotoxic T lymphocyte (CTL) and antibody responses induced by gene transfer. However, the IL-2-producing helper T lymphocyte (HTL) represents a critical regulatory cell that likely influences the inductive phase of the immune response following gene transfer. The current study employed limiting dilution analysis (LDA) techniques to characterize the development of IL-2-producing HTLs induced by genetic vaccination with a plasmid encoding the mutated HIV protein Rev M10. Further, we assessed the ability to inhibit the transgene-induced HTL response by cotransfer of a plasmid encoding the immunosuppressive cytokine TGFβ1.