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Self-Reactive T Cell Receptor-Reactive CD8⁺ T Cells Inhibit T Cell Lymphoma Growth In Vivo¹

Marie Gonthier^*, Régine Llobera^*, Jacques Arnaud^* and Bent Rubin^2,

^* Centre National de la Recherche Scientifique-Unité Propre de Recherche 2163, Centre-Hopital-Universitaire Purpan, Toulouse, France; and Unité Mixte Recherche 2587, Centre National de la Recherche Scientifique-Pierre Fabre, Toulouse, France

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- and TNF-, but little or no IL-4. By means of TCR-negative variant L12R4 cells, P3.3, and TCR-V2 cDNA-transfected and TCR-V2-expressing P3.3 lymphoma cells, we found that a significant part of the effector T cells are specific for the V12 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 V12 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-V-specific, K^b-, or D^b-restricted CD8⁺ T cells mediate inhibition of T cell lymphoma growth in vitro and in vivo.