Immunologic mechanisms in the pathogenesis of virus-induced leukemia. IV. Mechanism of target cell recognition by autoreactive thymocytes.
Neonatal infection of mice with Moloney murine leukemia virus (MuLV-M) results in the establishment of a chronic virus-carrier state. Such MuLV-carrier mice exhibit several immunologic abnormalities including generalized immunosuppression and autoimmunity. Previously, we found thymocytes from MuLV-M-carrier mice to be cytotoxic for normal syngeneic and allogeneic fibroblasts but not for xenogeneic (hamster) target cells. However, when the same syngeneic or allogeneic target cells were infected with MuLV-M, they were "spared" from the autoreactivity, leading us to speculate that the MuLV receptor on the target cell membrane was involved in the autoreactivity. To address this question, we tested MuLV-carrier thymocytes for their ability to lyse hamster/mouse-hybrid target cells; some of which possessed chromosome 5 (which codes for the ecotropic MuLV receptor). Of the nine hybrid cell lines initially tested, only the five clones that carried chromosome 5 were killed by the autoreactive thymocytes. In additional experiments, we noted that the cytotoxic reaction was inhibited in the presence of a monoclonal antibody that reacts with an MuLV-M gp70 epitope. The results suggest that the autoreactive cytotoxicity is mediated, at least in part, through the formation of a "bridge" between MuLV budding from the membrane of the thymocytes and the ecotropic MuLV receptor on the target cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D001667:Binding, Competitive; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000378:metabolism; D007942:Leukemia, Experimental / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008979:Moloney murine leukemia virus / Q000276:immunology / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000382:microbiology; D013950:Thymus Gland / Q000166:cytology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014760:Viral Fusion Proteins
D000911:Antibodies, Monoclonal; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins