TUMORIGENICITY OF MOUSE T-LYMPHOMA-CELLS IS CONTROLLED BY THE LEVEL OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I H-2K(K) ANTIGENS

We have previously found that an increased tumorigenicity and spontane ous metastatic potential of BW5147-derived T lymphoma cells was associ ated with a decrease in major histocompatibility complex (MHC) class I H-2K(k) antigen expression. This suggested that H-2K(k) antigens may control the tumorigenic potential of BW T lymphoma cells. Our current experiments aimed to prove this association by specifically altering H -2K(k) expression by gene transfection. Transfected cells expressing a high level of H-2K(k) antigens were significantly less tumorigenic an d metastatic after subcutaneous inoculation. However, there was select ion in vivo for cells expressing a reduced level of H-2K(k) antigens, which concomitantly led to an increased tumorigenicity. These data fur ther confirmed the strong association between H-2K(k) expression and t umorigenicity. We subsequently tested whether the immune system is imp licated in this phenomenon by inoculating the H-2K(k) transfectants in to irradiated, immunocompromised recipients. Our results indicate that the reduced tumorigenicity of the BW H-2K(k) transfectants is due to an immune rejection mechanism, mediated by CD8(+) immune effector cell s, as revealed by in vivo depletion experiments with anti-CDS antibodi es. Hence, we hereby demonstrated that H-2K(k) antigens increased the immunogenicity of BW cells, via a CD8-dependent mechanism, which conse quently reduced their tumorigenicity.