CORRELATION OF ONCOSTATIN-M SECRETION BY HUMAN RETROVIRUS-INFECTED CELLS WITH POTENT GROWTH-STIMULATION OF CULTURED SPINDLE CELLS FROM AIDS-KAPOSIS SARCOMA

Oncostatin M (OM), a 30-kDa glycoprotein, recently was identified as a major growth-promoting factor in the conditioned medium (CM) of the 3 8-0 cell line, a CD4,+ chronically human T lymphotropic virus type (HT LV)-II-infected, transformed T cell line. CM 38-0 induced the prolifer ation of spindle cells cultured in vitro from AIDS-associated Kaposi's sarcoma (AIDS-KS) cells. To determine how much of the AIDS-KS cell gr owth activity present in 38-0 CM was because of the presence of OM, we depleted OM by using specific mAb-affinity chromatography. OM purifie d from this CM stimulated AIDS-KS cell growth in a concentration-depen dent fashion. The effluent, completely depleted of OM, failed to induc e growth of AIDS-KS cells. To detect the constituitive release of OM b y cells acutely or chronically infected with either HTLV-I, HTLV-II, o r HIV-1, we utilized an enzyme-linked immunoassay. Whereas the chronic ally infected cells released significant levels of OM, the acutely inf ected cells released little or no OM. The presence of OM in HIV-1-infe cted T-cell CM correlated completely with AIDS-KS cell growth activity . Infrequently, low level AIDS-KS cell growth activity was seen in the absence of OM. This correlated with relatively high levels of IL-6 in the CM. In a CM-containing OM in the absence of detectable IL-6, a ne utralizing antibody to OM completely abrogated KS cell growth activity . The presence of specific oncostatin M receptors on the KS cell lines was confirmed by cross-linking experiments. The results shown here su ggest that T cells chronically infected with HIV-1 can secrete OM, whi ch may play a role in the initiation or progression of AIDS-KS lesions , either alone, or in concert with IL-6.