Metastasis of mouse T lymphoma cells is controlled by the level of major histocompatibility complex class I H-2D(k) antigens

In vivo inoculation of a low metastatic BW 5147 derived T-cell lymphoma variant into syngeneic mice, had led to the generation of a highly metastatic variant. The shift towards a more metastatic phenotype is accompanied by an increase in major histocompatibility class I H-2D(k) antigen expression. This suggests that H-2D(k) antigens may control the metastatic potential of BW T lymphoma cells. Our present findings indicate that H-2D(k) expression is directly correlated with the metastatic potential of BW cells. We have confirmed such correlation by specifically altering the lever of H-2D(k) expression by: 1) FACS analysis, 2) IFNγ treatment, 3) H-2D(k) gene transfection. Cells sorted for low H-2D(k) expression had a significantly reduced metastatic potential. Induction of H-2D(k) expression on these cells by either IFN-γ treatment or H-2D(k) gene transfection concomitantly led to increased metastasis. We also assessed metastatic potential of BW cells in irradiated, immunecompromised recipients. Our results show that the immune system is implicated and we further tested which immune effecters are involved. In vivo depletion of natural killer (NK) and CD8+ T-cells revealed that the difference in metastatic potential of the H-2D(k) variants relies upon an NK-dependent mechanism, whereas CD8+ T-cells are not implicated. Our observations suggest that highly metastatic cells, expressing a high level of H-2D(k) antigens are more resistant to NK-cell-mediated cytotoxicity in vivo. We have confirmed our in vivo results by in vitro cytotoxicity assays using poly I:C induced NK and IL-2 activated LAK cells. We conclude that a NK-dependent mechanism accounts for the association between differential H-2D(k) antigen expression and metastasis.SCOPUS: ar.jFLWNA