Immune response to Moloney murine leukemia virus nonviral, tumor-associated antigens fails to provide in vivo tumor protection.
Two distinct populations of CTL have previously been shown to be generated in lymphocyte cultures derived from the spleens of C57BL/6 mice that have rejected Moloney murine leukemia virus:Moloney sarcoma virus (MoMuLV:MSV)-induced tumors. One population is specific for MoMuLV viral Ag whereas the other appears to be directed against a nonviral, tumor-associated Ag (TAA). Using a virus-negative variant of the MoMuLV-induced lymphoma MBL-2 that has retained the expression of the MuLV:TAA, we attempted to further characterize the MuLV:TAA-specific CTL population. First, this same pattern of CTL reactivity was observed using a variety of immunization protocols indicating that the TAA-specific CTL population was not an artifact of the original immunization protocol but was a reproducible component of the MoMuLV CTL response. Moreover, CTL precursor frequency analysis indicates that the MuLV:TAA-specific CTL represent approximately 60% of the CTL detected in in vitro cytotoxicity assays. However, when the role of MuLV:TAA CTL in the in vivo rejection of MoMuLV-induced tumors was examined, no role for the MuLV:TAA-specific CTL response could be determined. Immunization protocols that had been shown to give rise to both CTL populations were capable of protecting mice from tumor development after a challenge with the parental MBL-2 tumor cell line but not the virus-negative variant MBLv cell line. In addition, immunization with the variant, shown to give rise to only MuLV:TAA-specific CTL capable of lysing both MBL-2 and MBLv in vitro, failed to protect mice from a tumor challenge of either cell type.
Jiang
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Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033.
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D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000032:analysis; D006410:Hematopoiesis; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D004279:DNA, Viral