Functional expression of CD43 on human natural killer cells

CD43 is the major leukocyte sialoglycoprotein that plays important function al roles in neutrophils and lymphocytes. However, the expression of CD43 on human natural killer (NK) cells and its participation hi the regulation of NK activity has not been studied. We have therefore investigated the expre ssion of CD43 isoforms on human NK cell subpopulations as well as the role of this molecule in NK cell activation and cytotoxicity. We found that CD56 (bright) and CD56(dim) NK cells express different sialylated forms of CD43, observing that activation of the CD56(bright) NK cells induces the change of tetrasaccharide O-glycans to hexasaccharide O-glycans on CD43. Cross-lin king of the molecule with mAbs results in a metalloprotease-dependent loss of CD43 from the NK cell surface, whereas soluble anti-CD43 mAbs induce a v igorous NK cell proliferation. This property is distinct from T cells, whic h proliferate after CD43 cross-linking only in the presence of monocytes. O ccupancy of the CD43 receptor on NK cells transduces specific signals, lead ing to enhanced killing activity and tyrosine phosphorylation and de-phosph orylation of several substrates. We therefore propose that CD43 significant ly contributes to the regulation of the NK cell function by participating i n the control of effector/target interactions and, if pertinent, by transdu cing activation signals.