title: Polyspecific self-reactive antibodies in individuals infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function.
abstract: Self-reactive polyspecific IgG antibodies (PSAs) arise in human immunodeficiency virus (HIV)-seropositive subjects before they develop AIDS. Self-reactive PSA levels correlate with the destruction of CD8 T cells in HIV-infected individuals and mediate the antibody-dependent cellular toxicity-based destruction of human T cells in tissue culture. PSAs react across the species barrier and bind to T cell antigens in mice. Such reactivity with mouse lymphocytes was not detected in normal human serum. Injection of human PSA IgG causes massive T cell depletion in the spleen, lymph nodes, and thymus in mice: evidence that PSA IgG facilitates T cell destruction in vivo. In addition to facilitating macrophage cytotoxicity, self-reactive PSA IgG inhibits the macrophage-mediated activation of T cells with antigen receptor-specific monoclonal antibody or with antigen. Exogenous costimulatory stimuli or interleukin (IL)-12 can reverse the inhibition. In contrast, exogenous IL-10 mimics this inhibition. These data implicate PSA IgG as a pathogenic factor in the development of HIV disease.
authors.affiliation: Departments of Microbiology, Immunology, New York Medical College, New York, USA.
authors.forename: Z q
authors.initials: Zq
authors.lastname: Wang
authors.forename: H W
authors.initials: HW
authors.lastname: Horowitz
authors.forename: T
authors.initials: T
authors.lastname: Orlikowsky
authors.forename: B I
authors.initials: BI
authors.lastname: Hahn
authors.forename: V
authors.initials: V
authors.lastname: Trejo
authors.forename: A S
authors.initials: AS
authors.lastname: Bapat
authors.forename: R S
authors.initials: RS
authors.lastname: Mittler
authors.forename: R J
authors.initials: RJ
authors.lastname: Rayanade
authors.forename: S Y
authors.initials: SY
authors.lastname: Yang
authors.forename: M K
authors.initials: MK
authors.lastname: Hoffmann
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood*; D018664:Interleukin-12 / Q000494:pharmacology; D008231:Lymphopenia / Q000097:blood / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012016:Reference Values
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12