Effect of IFN-gamma on the immune response in vivo and on gene expression in vitro

Abstract

T lymphocytes produce a variety of immunoregulatory molecules including gamma interferon (IFN-gamma) and antigen-specific suppressor and enhancer factors. During our studies of active substances obtained from cloned T-cell lines, we observed that certain fractions administered to mice resulted in enhancement of immune responses. Preliminary characterization of the substance suggested that it could be IFN-gamma and we therefore undertook a study of the action of IFN-gamma produced by recombinant DNA methodology on immune responses. We found that for several antigens, administration of IFN-gamma to mice leads to two- to five-fold enhancement of antibody formation provided that the IFN-gamma and antigen are administered together. The effect was dose dependent, giving a maximal response at 500-600 anti-viral units per mouse. Preliminary studies suggest that the macrophage may be the target of IFN-gamma action. Addition of IFN-gamma to cultures of a macrophage cell line leads to a greater than 10-fold increase in the level of RNA coding for I-region-encoded cell surface molecules.