Immunosuppression by metastatic lymphoma derived altered retroviral gp70 molecule.
In this report we describe the characteristics of an immunosuppressive molecule from an Abelson Leukemia Virus transformed highly malignant and metastatic RAW117-H10 murine large cell lymphoma cells. Our studies have shown that the mitomycin-c treated or irradiated RAW117-H10 cells very significantly (p < 0.001) inhibited the nitrogen induced proliferation of normal Balb/c splenocytes. The cell surface extracts from the immunosuppressive RAW117-H10 lymphoma cells significantly inhibited the in vitro T cell or NK/LAK cell functions. Our in vivo studies demonstrated that there was a significant suppression of immune response in the Balb/c mice bearing RAW117-H10 cells when compared with mice bearing low metastatic parental RAW117-P cells or control mice. Subsequently we isolated and purified the main molecule responsible for this immunosuppression and found that the molecule is a glycoprotein with a molecular weight of 70 kD with an isoelectric point of 4.3, which cross reacted with antibodies to murine leukemia virus envelope gp70 molecules. Further analysis using immunoelectrophoresis, molecular probing techniques, and mannose specific lectin binding assay revealed that the immunosuppressive 70 kD molecule, is different from the wild type MLV envelope gp70 molecule and thus appears to be an altered gp70 molecule. These studies demonstrate that the metastatic lymphoma associated immunosuppression may facilitate the growth and metastasis of tumor cells. Our results also elucidate the possible mechanism(s) of retrovirus induced immunosuppression and the molecular basis of this retroviral envelope-mediated process in viral pathogenesis and tumor progression.
Hao
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Department of Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha 68198-6395, USA.
Messbarger
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Joshi
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D000011:Abelson murine leukemia virus / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D015686:Gene Products, env / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D007165:Immunosuppression Therapy; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008264:Macrophages / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000494:pharmacology; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D015686:Gene Products, env; D006023:Glycoproteins; D014759:Viral Envelope Proteins; D016685:Mitomycin