IL-2andIL-7butnotIL-12protect natural killer cells fromdeathby apoptosis andup-regulate bcl-2 expression

SUMMARY Humannatural killer cells (NK)respond tointerleukin-2 (IL-2) withaugmented cytolytic activity, cytokine secretion andcell proliferation. Herewe showthatIL-2protects NK cells fromdeathby apoptosis (programmed cell death; PCD).Highly purified NK cells (CD3-CD56+)wereisolated fromperipheral bloodlymphocytes (PBL)ofeither control donors orofan asymptomatic donor with60%NK cells. Glucocorticosteroids (GCS)induced PCD inNK cells, asshownbynuclear condensation andDNA fragmentation. IL-2completely prevented GCS-induced PCD ina dosedependent manner without overcoming GCS-induced inhibition ofNK cell proliferation. TheIL-2 protective effect was mediated through thep75 chain oftheIL-2R, asneutralizing monoclonal antibody (mAb)tothep75Pchain butnottothep55achaincompletely abolished theIL-2antiapoptotic activity. Inaddition toIL-2, thecytokines IL-7andIL-12havebeenreported toregulate NK cell functions. Ourpresent datashowedthatIL-7butnotIL-12rescued NK cells from apoptosis, buttoalesser extent thanIL-2. Although IL-4hadamarginal protective effect, IL-1, IL-3, IL-6, IL-8, interferon-y (IFN-y) andIFN-a, tumournecrosis factor-a (TNF-a), transforming growthfactor-,B (TGF-P) andgranulocyte-macrophage colony-stimulating factor (GM-CSF)