RELEASE OF GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTORS FROM MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN-POSITIVE MONOCYTES IS ENHANCED BY HUMAN GAMMA INTERFERON

Abstract

Human gamma interferon (HuIFN.gamma.) was assessed for its capacity to enhance release of granulocyte-macrophage colony stimulating factors (GM-CSF) from human peripheral blood monocytes. Natural HuIFN.gamma. (2 .times. 107 NIH reference units per milligram) at concentrations as low as 0.01 U/mL to 10 U/mL reproducibly enhanced release of GM-CSF. This enhancement was detected when T lymphocytes were depleted from monocyte preparations and when T lymphocytes and monocytes were depleted from populations of human bone marrow cells stimulated by monocyte-conditioned media to form colonies and clusters. T lymphocytes alone or in the presence of HuIFN.gamma. did not release GM-CSF. The enhancing activity of HuIFN.gamma. was removed by preincubating HuIFN.gamma. with neutralizing concentrations of monoclonal anti-HuIFN.gamma., and recombinant HuIFN.gamma. mimicked the effects of natural HuIFN.gamma., suggesting that the effects were due to HuIFN.gamma. itself. HuIFN.gamma. suppression of the release of inhibitory activity from monocytes was ruled out as a reason for the noted enhancing activity of HuIFN.gamma.. The enhancing activity of HuIFN.gamma. was confined to the MHC class II antigen-positive population of monocytes. Removal of these cells with monoclonal antibody plus complement (C'') ablated the enhancing activity, high concentrations of certain monoclonal antibodies in the absence of C'' blocked the enhancing activity and, when monocytes were sorted into MHC class II antigen-positive and -negative cells by fluorescence-activated cell sorting, it was only the positive cell fraction that responded to the enhancing activity of HuIFN.gamma.