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.

Abstract

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.

• Authors: A Yoshimura, H Shiku, E Nakayama
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 150 Issue 11 Pg. 4900-10 (Jun 01 1993) ISSN: 0022-1767 [Print] United States
• PMID: 8496592 (Publication Type: Journal Article)

Chemical References

• CD4 Antigens
• CD8 Antigens
• Histocompatibility Antigens Class II
• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Animals
• Antibody Specificity
• Binding Sites, Antibody
• CD4 Antigens (analysis)
• CD8 Antigens (analysis, physiology)
• Clone Cells (chemistry)
• Cytotoxicity, Immunologic
• Flow Cytometry
• Friend murine leukemia virus
• Genetic Variation (immunology)
• Graft Rejection
• Histocompatibility Antigens Class II (analysis)
• Immunotherapy, Adoptive
• Leukemia, Erythroblastic, Acute (immunology)
• Lymphocyte Depletion
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Receptors, Antigen, T-Cell, alpha-beta (analysis)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured