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CD56 bright natural killer cell subsets: Characterization of distinct functional responses to interleukin‐2 and the c‐kit ligand

1997; Wiley; Volume: 27; Issue: 2 Linguagem: Inglês

10.1002/eji.1830270203

1521-4141

William E. Carson, Todd A. Fehniger, Michael A. Caligiuri,

Immunotherapy and Immune Responses

Abstract Natural killer (NK) cells are bone marrow‐derived large granular lymphocytes that express the CD56 surface antigen. The CD56 bright NK subset represents approximately 10 % of all NK cells and is thought to be the least differentiated NK cell component in blood. The most mature NK cell expresses CD56 at low density and CD16 (FcRγIII) at high density, whereas CD56 bright NK cells either lack CD 16 (CD56 bright CD16 − ) or express it at low density (CD56 bright CD16 dim ). c‐kit is a tyrosine kinase receptor which is expressed on both CD34 + hemato‐poietic precursor cells and CD56 bright NK cells. In the current study, we characterize interleukin (IL)‐2 receptor (IL‐2R) and c‐kit expression in each of the CD56 bright subsets. Both the CD56 bright CD16 − and CD56 bright CD16 dim NK subsets express the high‐affinity IL‐2R and the c‐kit receptor when isolated from fresh blood. However, each CD56 bright NK cell subset has distinct functional responses to IL‐2, the c‐kit ligand (KL), or both. Activation of the high‐affinity IL‐2R on CD56 bright CD16 − NK cells induces a proliferative response that is significantly weaker than that observed in the CD56 bright CD16 dim NK cell subset. Incubation of the CD56 bright CD16 − NK cell subset with KL significantly enhances IL‐2‐induced proliferation, while KL has no such effect on the CD56 bright CD16 dim NK subset. Activation of the high‐affinity IL‐2R in both CD56 bright subsets induces lymphokine‐activated killer (LAK) activity, but the addition of KL has no effect on LAK activity. Co‐stimulation of either CD56 bright subset with IL‐12 and concentrations of IL‐2 that only saturate the high‐affinity IL‐2R induces substantial interferon (IFN)‐γ production. The addition of KL to this co‐stimulatory signal enhances IFN‐γ production in both CD56 bright NK subsets. The distinct functional responses to IL‐2 and KL seen in the CD56 bright CD16 − and CD56 bright CD16 dim NK subsets provide insight into IL‐2R signaling and suggest that each phenotype identifies a discrete stage of NK cell differentiation.