Participation of CD45 on pit cells and MHC class I on target cells in rat hepatic NK cell (pit cell)-mediated cytotoxicity against colon carcinoma cells

Cytotoxic activity of natural killer (NK) cells is believed to be regulated by triggering and inhibitory receptors on NK cells. Several different trig gering receptors have been described to be involved in NK cell-mediated tar get cytotoxicity. In ail these studies NK cells were used, derived from blo od or spleen. Pit cells are liver specific NK cells. They possess a higher level of natural cytotoxicity and different morphology when compared to blo od NK cells. The aim of this study was to characterize the role of the NK-r egulating molecules NKR-P1, ANK61 antigen and CD45 in pit cell-mediated kil ling of target cells. Cr-51-release and DNA fragmentation were used to quan tify target cell lysis and apoptosis. Flow cytometric analysis showed that pit cells expressed CD45, NKR-P1 and ANK61 antigen. CC531s cell, expressed MHC class I molecules. Treatment of freshly isolated rat pit cells with mAb s to CD45 not only inhibited CC531s target lysis but also apoptosis. Treatm ent of CC531s with mAb directed against MHC class I increased the CC531s ce ll lysis and apoptosis by pit cells. The mAbs to NKR-P1 (3.2.3) and ANK61 a ntigen (ANK61) had no effect on pit cell-mediated CC531s cytolysis or apopt osis. However, mAbs 3.2.3 and ANK61 increased pit cell-mediated Fc gamma R P815 cytolysis, These results indicate that CD45 on pit cells and MHC clas s I on CC531s cells participated in pit cell-mediated CC531s cytolysis and apoptosis. Furthermore, NKR-P1 and ANK61 antigen on pit cells function as a ctivation structures. These findings provide evidence that the same molecul es on pit cells as on blood or spleen-derived NK cells regulate target cell lysis and apoptosis. The difference in cytotoxicity capacity between these cell types therefore may be on a quantitative rather than a qualitative le vel.