GENETIC VACCINATION-INDUCED IMMUNE-RESPONSES TO THE HUMAN-IMMUNODEFICIENCY-VIRUS PROTEIN REV - EMERGENCE OF THE INTERLEUKIN 2-PRODUCING HELPER T-LYMPHOCYTE

Rev M10 is a trans-dominant negative inhibitor of HIV replication. Hen ce, stable transduction of CD4(+) T cells with Rev M10 represents a no vel gene therapy aimed at inhibiting HIV replication within these cell s, thereby slowing the progression of AIDS. However, the immune system may recognize Rev M10 as foreign and target transduced cells for elim ination. In the current study, mice were genetically immunized with a plasmid encoding Rev M10, to (1) identify immune parameters that may b e induced by Rev M10 gene transfer, (2) determine the impact of repeat ed introduction of the Rev M10-encoding plasmid on the immune response to the transgene product, and (3) determine if cotransfection with a plasmid encoding TGF beta 1 would suppress the response, Kinetic studi es revealed that Rev-specific IL-2-producing helper T lymphocytes (HTL s) appeared following the second genetic immunization, peaked after th e third, and persisted at peak levels for at least 6 weeks. Rev-specif ic HTLs were CD4(+), and the development of these cells was ablated by cotransfection with TGF beta 1, Other cytokines were not readily dete ctable when immune splenocytes were restimulated with Rev in vitro, an d Rev-specific Ige antibodies were not present in the sera of these mi ce. To our knowledge, this represents the first report that genetic im munization with Rev M10 induces an immune response that is dominated b y IL-2-producing HTLs. Further, this study demonstrates the potential utility of introducing immunosuppressive genes as a means to control t he immune response to foreign transgene products.