INTRINSIC RESISTANCE TO T-CELL INFECTION WITH HIV TYPE-1 INDUCED BY CD28 COSTIMULATION

When HIV-infected leukocytes are activated by the CD28 costimulatory r eceptor, HIV-1 is rapidly cleared from cultures, suggesting that costi mulation can render T cells resistant to HIV-1 infection, In this stud y we tested the hypothesis that enhanced secretion of cytokines or che mokines could account for CD28-induced antiviral effects. In an acute infection system, resistance to infection with macrophage-tropic strai ns of HIV-1 was shown to be comprised of both soluble and cell-associa ted components, Induction of HIV-1 resistance was specific for CD28 co stimulation, in that a variety of other accessory receptors, such as C D2, CD4, CD5, and MHC class I, failed to confer the antiviral resistan ce, The soluble component was secreted by both CD4 and CD8 T cells, wa s not unique to CD28 costimulation, and could be neutralized by remova l of C-C chemokines (RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1 alpha an d -1 beta) from the culture supernatants of costimulated CD4 T cells, In contrast, CD28 stimulation of CD4 cells resulted in the specific in duction of a pronounced intrinsic resistance to HIV-1 infection by mac rophage tropic isolates of HIV-1.