Autoimmunity and counter-autoimmunity in the mechanisms of retrovirus-induced leukemogenesis.
The role of autoimmune mechanisms in the pathogenesis of retrovirus-induced leukemia was studied using as models different forms of Rauscher leukemia virus (RV) infection in mice of different strains. It was found that mice undergoing progressive course of leukemia ("progressors") produce (a) autoantibodies to a series of antigens intimately involved on immune response regulation (class II MHC antigens, cell surface markers of helper and suppressor T-lymphocytes and erythrocaryocytes, receptors for IL-2, etc.); (b) antiidiotypic antibodies which suppress both antiviral responses and autoimmune reactions against class I MHC antigens. Passive transfer of these antibodies into genetically resistant mice prior to RV inoculation breaks their resistance. Completely resistant C57BL/6 mice and mice undergoing "spontaneous" regression of leukemia ("regressors") were found to be genetically capable of (a) suppressing autoimmune reactions of "progressors" type by active synthesis of antiidiotypic antibodies; (b) producing autoantibodies to MHC class I antigens. Immunization with monoclonals to H-2Db as well as with "anti-autoimmune" antiidiotypes prior to RV infection leads to abrogation of appropriate immune reactions and development of leukemia in C57BL/6 mice.
Ter-Grigorov
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Department of Immunology, Kimron Veterinary Institute, Bet-Dagan, Israel.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007942:Leukemia, Experimental / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011925:Rauscher Virus / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G