Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation.
Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study.
D000818:Animals; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000032:analysis*; D016026:Bone Marrow Transplantation; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000032:analysis; D007111:Immunity, Cellular; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR / Q000276:immunology*; D008810:Mice, Inbred C57BL / Q000276:immunology*; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D006183:H-2 Antigens