title: IFN increases class I MHC antigen expression on adenovirus-infected human cells without inducing resistance to natural killer cell killing.
abstract: It has been previously shown that unstimulated NK cells cannot preferentially lyse adenovirus serotypes 2 and 5-infected human cells. In this study, the ability of IFN to promote the selective NK cell-mediated lysis of adenovirus-infected human cells was determined. The relationship between target cell susceptibility to NK cell-mediated killing and class I Ag expression was also analyzed through the use of adenovirus serotype 2 and 5 mutants that do not make the adenovirus early region 3 19-kDa class I binding protein. IFN induced the selective lysis of adenovirus serotype 2 and 5-infected human cells by activating NK cells (IFN-alpha) and protecting uninfected, but not adenovirus-infected cells, from NK cell-mediated lysis (IFN-gamma). IFN-gamma increased the expression of class I Ag on the surface of cells infected with the adenovirus early region 3 deletion mutants, dl327 or dl801, to a level equal to or greater than that expressed on uninfected cells. Despite the increased expression of class I Ag, IFN-gamma could not protect these adenovirus-infected cells from NK cell-mediated lysis. Thus, dl327 or dl801 infection prevented IFN-gamma's induction of cytolytic resistance to NK cell-mediated killing but left IFN-gamma's induction of class I Ag intact. Surface class I Ag levels were substantially higher on IFN-gamma-treated, dl327-, and dl801-infected cells in comparison to cells infected with wild type adenovirus serotype 5. Again, higher target cell levels of class I Ag did not correlate with increased resistance to NK cell-mediated lysis because there was equivalent NK cell-mediated killing of IFN-gamma-treated adenovirus serotype 5-, dl327-, or dl801-infected cells. Thus, IFN-gamma only protects uninfected cells from NK cell-mediated killing, irrespective of target class I Ag levels, and thereby concentrates NK lytic activity on just adenovirus-infected cells. These data demonstrate that IFN-gamma's ability to protect target cells from NK cell-mediated cytolysis is unrelated to IFN-gamma's induction of surface class I MHC Ag.
authors.affiliation: Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: J M
authors.initials: JM
authors.lastname: Routes
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology; D000260:Adenoviruses, Human / Q000502:physiology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D007372:Interferons