IL-12-MEDIATED ACTIVATION OF MHC-UNRESTRICTED CYTOTOXICITY OF HUMAN PBMC SUBPOPULATIONS - SYNERGIC ACTION OF A PLANT RHAMNOGALACTURONAN

IL-12 mediated activation of human MHC-unrestricted cytotoxicity was s tudied with freshly isolated, highly enriched CD56(+)CD3(-) NK cells ( 95-98%), monocytes/macrophages (90-95%) and CD3(+)T cells (95-98%). Ac tivation of NK cell cytotoxicity and monocyte cytotoxicity by IL-12 we re independent of exogenous IL-2 and IFN gamma. Activation of CD3(+)T cells to MHC-unrestricted cytotoxicity required coactivation by anti-C D3 antibody. The enhanced cytotoxicities were directed against NK-sens itive as well as NK-resistant target cells and coincided with enhancem ent of effector cell/target cell conjugate formation. The specific cyt otoxicity of all three activated effector cell populations was further increased in the presence of rhamnogalacturonan. These increases were based on an additional increase of effector cell/target cell conjugat e formation that is based on rhamnogalacturonan-mediated bridging betw een effector cells and target cells. Simultaneous enhancement of cytot oxicity indicates involvement of receptors on effector cells cross-rea cting with acetylrhamnose (6-deoxymannose) that might play an importan t role in human MHC-unrestricted cytotoxicity against tumor cells.