Self-reactive T cell receptor-reactive CD8+ T cells inhibit T cell lymphoma growth in vivo.
Syngenic C57BL/6 mice (H-2(b)) vaccinated with mitomycin C-treated L12R4 T lymphoma cells develop protective immunity toward the MHC class II-negative tumor cells. In the present study, we characterize the nature, mode of function, and specificity of the effector cells in this immunity. These cells are TCR-specific CD8(+) T lymphocytes with effector function in vitro as well as in vivo upon transfer to naive mice. They produce high levels of IFN-gamma and TNF-alpha, but little or no IL-4. By means of TCRbeta-negative variant L12R4 cells, P3.3, and TCR-Vbeta2 cDNA-transfected and TCR-Vbeta2-expressing P3.3 lymphoma cells, we found that a significant part of the effector T cells are specific for the Vbeta12 region. The growth inhibition of L12R4 cells in vitro was inhibited by anti-H-2, anti-K(b), and anti-D(b) mAb. Furthermore, vaccination with Vbeta12 peptide p67-78, which binds to both K(b) and D(b) MHC class I molecules, induces partial protection against L12R4 T lymphoma cells. Thus, self-reactive TCR-Vbeta-specific, K(b)-, or D(b)-restricted CD8(+) T cells mediate inhibition of T cell lymphoma growth in vitro and in vivo.
Gonthier
Marie
M
Centre National de la Recherche Scientifique-Unité Propre de Recherche 2163, Centre-Hopital-Universitaire Purpan, Toulouse, France.
Llobera
Régine
R
Arnaud
Jacques
J
Rubin
Bent
B
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007939:Leukemia L1210; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma