Natural antibodies to interferon-gamma

Natural antibodies to interferon (IFN)-γ 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-γ 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-γ production as a result of antigenic stimulation in vivo. Natural antibodies to IFN-γ 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-γ antibodies have no inhibitory effect on the antiviral and antiproliferative activity of IFN-γ 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-γ 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-γ 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-γ, these antibodies might open up new therapeutic approaches to diseases with evidence of activated cell-mediated immunity.