Polyspecific self-reactive antibodies in individuals Infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function

Self-reactive polyspecific IgG antibodies (PSAs) arise in human immunodefic iency virus (HIV)-seropositive subjects before they develop AIDS. Self-reac tive PSA levels correlate with the destruction of CD8 T cells in HIV-infect ed individuals and mediate the antibody-dependent cellular toxicity-based d estruction of human T cells in tissue culture; PSAs react across the specie s barrier and bind to T cell antigens in mice. Such reactivity with-mouse l ymphocytes was not detected in normal human serum. Injection of human PSA I gG causes massive T cell depletion in the spleen, lymph nodes, and thymus i n mice: evidence that PSA IgG facilitates T cell destruction in vivo. In ad dition to facilitating macrophage cytotoxicity, self-reactive PSA IgG inhib its the macrophage-mediated activation of T cells with antigen receptor-spe cific monoclonal antibody or with antigen. Exogenous costimulatory stimuli or interleukin (IL)-12 can reverse the inhibition. In contrast, exogenous I L-10 mimics this inhibition. These data implicate PSA IgG as a pathogenic f actor in the development of HIV disease.