RESTORATION OF HIV-SPECIFIC CELL-MEDIATED IMMUNE-RESPONSES BY INTERLEUKIN-12 IN-VITRO

Peripheral blood mononuclear cells (PBMCs) from many asymptomatic indi viduals infected with human immunodeficiency virus-type 1 (HIV) are un responsive as measured by in vitro T cell proliferation and interleuki n-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 respo nses and T cell proliferation were restored when cultures were stimula ted in the presence of IL-12. Interferon-gamma production by PBMCs fro m HIV seropositive (HIV+) patients was also restored with IL-12. Furth ermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but w ere not enhanced by addition of exogenous IL-12. Thus, IL-12 may be li miting in PBMCs from HIV+ but not HIV- individuals. These findings dem onstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-1 2 in augmenting the diminished immunologic functions associated with H IV infection.