CONSTITUTIVE PRODUCTION OF NOVEL MACROPHAGE-ACTIVATING FACTOR(S) BY HUMAN T-CELL HYBRIDOMAS

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1-alpha, human-interleukin-1-beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.