Rejection of an IA+ variant line of FBL-3 leukemia by cytotoxic T lymphocytes with CD4+ and CD4-CD8- T cell receptor-alpha beta phenotypes generated in CD8-depleted C57BL/6 mice.
FBL-3N is an MHC class II Ag+ variant line that was obtained spontaneously during maintenance of Friend virus-induced leukemia FBL-3 in an athymic C57BL/6 (B6) mouse. Inocula of FBL-3N, but not the parental FBL-3 tumor, regressed after initial growth in CD8-depleted, syngeneic B6 mice. The cellular mechanisms by which FBL-3N was rejected in these mice were investigated in this study. We demonstrated that CTL with both CD4+ and CD4-CD8-TCR-alpha beta phenotypes were generated in mixed lymphocyte tumor cell culture spleen cells obtained from CD8-depleted B6 mice that had rejected FBL-3N by in vitro stimulation with mitomycin C-treated FBL-3N. After adoptive transfer of these CTL that were generated in vitro into athymic B6 mice, challenge with the FBL-3N tumor resulted in tumor regression after its initial growth. Thus, CD4+ and CD4-CD8-TCR-alpha beta CTL mediated rejection of the FBL-3N tumor in CD8-depleted B6 mice. Furthermore, the findings that depletion of B6 mice of CD4+ cells in addition to CD8+ cells abrogated the rejection of FBL-3N and generation of CTL in mixed lymphocyte tumor cell culture spleen cells suggest that CD4+ cells were required not only as a source of CD4+ CTL, but also as helper cells for generation of CD4-CD8-TCR-alpha beta CTL. Tumor Ag recognition of CD4-CD8-TCR-alpha beta CTL was restricted to Db, like that of classical CD8+ CTL, but the restriction appeared to be less obligatory than that of CD8+ CTL.
Department of Periodontology, Nagasaki University School of Dentistry, Japan.
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Yoshimura
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H
Shiku
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Nakayama
D000818:Animals; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis* / Q000502:physiology; D002999:Clone Cells / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005622:Friend murine leukemia virus; D014644:Genetic Variation / Q000276:immunology; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D016219:Immunotherapy, Adoptive; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta