ROLES OF CHEMOKINES AND RECEPTOR POLARIZATION IN NK-TARGET CELL-INTERACTIONS

We report that the ability of NK cells to produce chemokines is increa sed in NK-target cell conjugates, The chemokines produced play a criti cal role in the polarization and recruitment of NK cells as well as in the NK effector-target cell conjugate formation. Chemokines induce th e formation of two specialized regions in the NK cell: the advancing f ront or leading edge, where chemokine receptors CCR2 and CCR5 cluster, which might guide the cells toward the chemotactic source, and the ur opod, where adhesion molecules ICAM-1 and -3 are redistributed. NK cel l polarity was intrinsically involved in conjugate formation. The redi stribution of both adhesion receptors and CCR was preserved during the formation of NK-target cell conjugates, Time-lapse videomicroscopy st udies of the formation of effector-target conjugates showed that morph ologic poles are also functionally distinct; while the binding to targ et cells was preferentially mediated through the leading edge, the uro pod was found at the rear of migrating NK cells and recruited addition al NK cells to the vicinity of K562 target cells. Inhibition of cell p olarization and adhesion receptor redistribution blocked the formation of NK-K562 cell conjugates and the cytotoxic activity of NK cells. We discuss the implication of NK-cell polarization in the development of cytotoxic responses.