Expression and function of α4/β7 integrin on human natural killer cells

In this report, we have analysed the expression and function of the α4/β7 heterodimer in human natural killer (NK) cells. The expression of α4β7 is induced in NK cells upon activation, as the anti‐α4β7 ACT‐1 monoclonal antibody (mAb) faintly stained a minority of peripheral blood NK cells, whereas it strongly reacted with in vitro long‐term interleukin‐2 (IL‐2)‐activated NK cells. Incubation with ACT‐1 or its F(ab′)2 fragments induced a strong homotypic adhesion of NK cells, comparable to that stimulated by the anti‐α4 HP1/7 mAb. Cell–cell interaction induced by the ACT‐1 mAb was only prevented by another anti‐α4 mAb (HP2/1) that recognizes a different epitope. In α4β7‐mediated cell aggregation, the α4β7 heterodimer was redistributed to intercellular contact sites, thus, suggesting a direct involvement of this integrin in the formation of cell clusters. In NK cells attached to Fibronectin (FN38) or vascular cell adhesion molecule‐1 (VCAM‐1), both α4β7 and α4β1 integrins were redistributed at the ventral cellular membrane forming discrete contact sites. The ACT‐1 mAb only partially blocked NK cell binding to FN38, but in combination with the anti‐β1 mAb LIA1/2, NK cell binding to FN38 was completely inhibited. In contrast, ACT‐1 did not modify NK cell adhesion to VCAM‐1, thus supporting the theory that the α4β7 binding sites for both ligands appear to be different. Our results indicate that upon IL‐2‐activation, expression of functional α4/β7 integrin is induced on NK cells, potentially participating in their interaction with both extracellular matrix and endothelial cells.