title: Intrinsic resistance to T cell infection with HIV type 1 induced by CD28 costimulation.
abstract: When HIV-infected leukocytes are activated by the CD28 costimulatory receptor, HIV-1 is rapidly cleared from cultures, suggesting that costimulation can render T cells resistant to HIV-1 infection. In this study we tested the hypothesis that enhanced secretion of cytokines or chemokines could account for CD28-induced antiviral effects. In an acute infection system, resistance to infection with macrophage-tropic strains of HIV-1 was shown to be comprised of both soluble and cell-associated components. Induction of HIV-1 resistance was specific for CD28 costimulation, in that a variety of other accessory receptors, such as CD2, CD4, CD5, and MHC class I, failed to confer the antiviral resistance. The soluble component was secreted by both CD4 and CD8 T cells, was not unique to CD28 costimulation, and could be neutralized by removal of C-C chemokines (RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha and -1beta) from the culture supernatants of costimulated CD4 T cells. In contrast, CD28 stimulation of CD4 cells resulted in the specific induction of a pronounced intrinsic resistance to HIV-1 infection by macrophage tropic isolates of HIV-1.
authors.affiliation: Division of Retrovirology, Walter Reed Army Institute for Research, Rockville, MD 20850, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Riley
authors.forename: R G
authors.initials: RG
authors.lastname: Carroll
authors.forename: B L
authors.initials: BL
authors.lastname: Levine
authors.forename: W
authors.initials: W
authors.lastname: Bernstein
authors.forename: D C
authors.initials: DC
authors.lastname: St Louis
authors.forename: O S
authors.initials: OS
authors.lastname: Weislow
authors.forename: C H
authors.initials: CH
authors.lastname: June
mesh_terms: D018106:CD28 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007113:Immunity, Innate; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I