Tumor immune escape by immunoregulatory CD4 T cells

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Cancer immune surveillance theory has been widely accepted, but the scientific basis is still obscure. Tumor immune escape is also a theory of which mechanisms have not fully elucidated. Recently, tumor antigens recognized by the host immune system have been identified at molecular level, and the analysis of tumor immune responses against the tumor immunology, theories of the immune surveillance and the tumor immune escape should be carefully reevaluated.In this study, using BALB/c radiation leukemia RL♂1 on which we previously identified the antigen peptide recognized by the specific CTL as a model tumor, we identified tumor antigen specific regulatory CD4 T cells. We showed that altered Akt molecule which is dominant antigen in RL♂1 stimulated immunoregulatory CD4 T cells and inhibited efficient generation of CD8 CTL which recognized the tumor antigen peptide derived also from the Akt molecule.Beside those tumor antigen specific regulatory CD4 T cells, we also found immunoregulatory CD4ィイD1+ィエD1CD25ィイD1+ィエD1 T cells which were tumor antigen non-specific. Those cells were activated by autoantigens and protected from auto immunity. We showed that by in vivo depletion of CD4ィイD1+ィエD1CD25ィイD1+ィエD1 T cells, efficient tumor rejection response occurred.