Human gamma interferon production by leukocytes induced with monoclonal antibodies recognizing T cells

Abstract

The murine monoclonal antibody OKT3 (IgG2), which recognizes the majority of human E-rosette-forming cells, was found to induce interferon (IFN) production in human peripheral lymphocytes in vitro. This IFN was classified as IFN-gamma by virtue of its acid stability, nonneutralization by antisera recognizing human IFN-alpha and beta, and non-cross-reactivity on bovine kidney cells. OKT3 elicited considerable IFN-gamma yields at a concentration of 1 ng/ml, at which only very low mitogenesis of the lymphocytes measured by 3H-thymidine incorporation was seen. The IFN-gamma activity appeared beginning 3 to 6 hr after stimulation and reached its maximum after 36 hr. Anti-human Lyt3, anti-human Lyt2, or anti-human Lyt1 monoclonal antibodies, recognizing all or the majority of the E-rosette-forming cells, did not elicit IFN-gamma production. The OKT4 monoclonal antibody, which defines a subpopulation of T cells containing cells with helper activity, induced marginal levels of IFN-gamma. In contrast, OKT8 monoclonal antibody (defining cytotoxic/suppressor cells) as well as monoclonal or heterologous antibodies recognizing histocompatibility antigens or surface immunoglobulin failed to induce IFN-gamma production. Heterologous anti-thymocyte globulin or anti-lymphocytic serum were effective IFN-gamma inducers. Cell separation studies of the leukocytes demonstrated that E-rosette-forming cells are responsible for production of IFN-gamma induced by OKT3. Treatment of the leukocyte suspension with OKt3 monoclonal antibody plus complement abolished IFN-gamma production induced by this antibody. These results demonstrate that the OKT3 antibody recognizing an antigen present on the majority of the E-rosette-forming cells alone is sufficient to induce IFN-gamma production. OKT3-positive cells are apparently the producers of this IFN-gamma.