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Regulation of Natural Killer Cell Co-stimulation by TNF Superfamily Members

Upon activation, natural killer (NK) cells secrete cytotoxic and inflammatory cytokines that cause apoptosis or lysis of targeted cells. While some pathogens can directly activate NK cells, NK cells are indirectly activated in response to most pathogens by accessory cells. Several TNF superfamily members have been implicated in mediating NK cell activation and regulation by accessory cells. These members include 4-1BB, CD27, CD30, GITR, and CD40 and their respective ligands, as well as HVEM via LIGHT and TNF RII via TNF-alpha. NK cells also express Fas Ligand and TNF-alpha on their cell surface that, when bound to target cell-expressed Fas or TNF RI, respectively, initiate caspase-mediated apoptosis of the target cell.