Differential expression and function of L-selectin on CD56(bright) and CD56(dim) natural killer cell subsets

NK cells are the first line of defense against foreign cells, virally infected cells, and tumors. The mechanisms whereby NK cells accumulate in extralymphoid sites in response to pathogenic stimuli are not well understood. The L-selectin adhesion molecule (CD62L) plays a primary role in mediating the initial interaction of leukocytes with vascular endothelium, a crucial step in the extravasation of immune effector cells into tissues. In this report, we show L-selectin to be uniquely expressed on a subset of resting human NK cells (CD56(bright)). Notably, CD56(bright) NK cells expressed L-selectin at a higher density than all other peripheral blood leukocytes. NK activation by PMA, IL-2, IL-15, or TGF-β down-regulated L- selectin on the CD56(bright) subset, while increased L-selectin levels were observed in both the CD56(bright) and CD56(dim) NK subsets in response to IL- 12, IL-10, or IFN-α. Moreover, CD56(bright) NK cells bound with high efficiency to physiologic L-selectin ligands on peripheral lymph node high endothelial venules (HEV). In sharp contrast, CD56(dim) NK cells adhered poorly to HEV and were predominantly L-selectin- or expressed L-selectin only at low density. In CD56(bright) cells and a subpopulation of CD56(dim) cells, L-selectin ligation by mAb cross-linking activated lymphocyte function- associated Ag 1 (LFA-1), a second adhesion molecule required for leukocyte extravasation. LFA-1 was expressed on both NK subsets, although its density was constitutively higher on CD56(dim) cells. Taken together, evidence of differential expression of L-selectin and LFA-1 on CD56(bright) and CD56(dim) NK subsets strongly suggests unique migratory properties and functions of these cells during the early immune response to foreign pathogens.