Natural antibodies to interferon-gamma

Natural antibodies to interferon (IFN)-gamma were detected in the serum of virus-infected patients and also, at a low titre, in the serum of healthy subjects. The increased titre of antibodies to IFN-gamma in the sera of virus-infected patients, and its decrease with clinical resolution, indicate that these antibodies are related to viral infection and probably reflect IFN-gamma production as a result of antigenic stimulation in vivo. Natural antibodies to IFN-gamma were affinity purified and studied for their capability to interfere in vitro with the multiple activities of the lymphokine. Data obtained show that these human anti-IFN-gamma antibodies have no inhibitory effect on the antiviral and antiproliferative activity of IFN-gamma and do not interfere with the binding of the lymphokine to its specific cell receptor. Instead, they can inhibit the expression of HLA-DR antigens induced by IFN-gamma on U937 cells and interfere, in mixed lymphocyte culture, with the proliferation of lymphocytes and the generation of cytotoxic lymphocytes. Experiments in animal models suggest that natural antibodies to IFN-gamma may have a role in the immunoregulatory process limiting the intensity and/or duration of immune response. As they can interfere only with the immunomodulating activities of IFN-gamma, these antibodies might open up new therapeutic approaches to diseases with evidence of activated cell-mediated immunity.