CD56^dimCD16⁺ NK cells downregulate CD16 following target cell induced activation of matrix metalloproteinases

Natural killer (NK) cells are immune effector cells that recognize both virally infected and malignant target cells. Unlike T and B cells, NK cells do not belong to the adaptive immune system, and their activation and cytotoxicity is regulated via a series of non-rearranged cell surface receptors. These receptors transmit either activating or inhibitory signals, the summation of which is thought to dictate whether NK cell activation occurs or not. Functionally NK cells are able to kill target cells without prior sensitization and release potent pro-inflammatory cytokines such as interferon (IFN) and tumor necrosis factor (TNF). Discrete NK cell subsets can be identified in peripheral blood on the basis of CD56 and CD16 staining (reviewed by Cooper et al.¹). CD56^brightCD16^−/+ cells are more potent producers of IFN-γ in response to monokine stimulation and reciprocally interact with dendritic cells, leading to the activation of both cell types, whereas CD56^dimCD16⁺ NK cells show higher cytotoxicity against malignant targets. By definition, NK cells lack the expression of CD3 and the T-cell receptor. CD3⁺CD56⁺ cells are present in the peripheral blood (PB) and as these cells belong to the T-cell lineage, they share phenotypic and functional properties with NK cells.² When studying NK cells the interference of these NK-like T cells should be excluded.

One of the main mechanisms of target cell killing is through the granule release pathway. Following target cell conjugation and NK activation, cytotoxic granules move toward the cell surface, fuse with the cell membrane and the granule contents (including perforin and granzymes) are expelled into the synaptic junction between the effector and target cells. Until recently, it has not been possible to identify individual effector cells that have extruded their granule contents. However, recent studies show that specific membrane proteins, such as CD107a (lysosome-associated membrane protein 1, LAMP-1) are located within the cytotoxic granule membrane and are transiently expressed on the cell surface following degranulation. Monoclonal antibody (mAb) against CD107a identifies cells that have recently released their granule contents.³