Natural human antibodies to gamma interferon interfere with the immunomodulating activity of the lymphokine.

Natural antibodies to γ interferon (IFN-γ) were found in patients suffering from different viral diseases and, at a lower titer, in healthy individuals. Such antibodies were affinity-purified and studied for their capability to interfere in vitro with the antiviral and immunomodulating activity of IFN-γ. Data obtained show that these human anti-IFN-γ antibodies have no inhibitory effect on the antiviral activity of IFN-γ. On the contrary, they are able to inhibit the expression of Fc receptor sites and HLA-DR antigens induced by IFN-γ on the U-937 cells, a human monocytoid/macrophage-derived cell line. These antibodies can also interfere in a mixed lymphocyte culture (MLC) with the proliferation of lymphocytes and the generation of cytotoxic lymphocytes. However, they showed only a moderate inhibitory effect on the cytotoxicity generated in MLC to K-562 cells. Human antibodies capable of interfering with the immunomodulating activities of IFN-γ might open up a new field in clinical therapy for those diseases that carry evidence of activated cell-mediated immunity.