Target cell directed NK inactivation. Concomitant loss of NK and antibody-dependent cellular cytotoxicity activities.
We investigated the inactivation of human NK cells, a population of large granular lymphocytes (LGL), with K562, an NK-sensitive target cell (TC) and KLCL, an NK-resistant TC, but which can be lysed by NK cells via antibody (Ab)-dependent cellular cytotoxicity. NK-enriched effector cells (ECc) were first treated with either K562 or Ab-coated KLCL (Ab-KLCL). After incubation, ECc were separated from their TC then examined for residual NK and ADCC activities, phenotypic changes, and changes in LGL morphology. K562-treated ECc and Ab-KLCL-treated ECc, when retested against the inactivating TC, respectively, lost greater than 90% of their lytic activities. However, K562-treated ECc lost 60 to 70% of their activity against Ab-KLCL, whereas Ab-KLCL-treated ECc lost less than 10% of their activity against K562. In contrast to what we observed with K562-treated ECc, we detected significant reductions in plasma membrane expression of Leu-11a and Leu-11b on Ab-KLCL-treated ECc. Although the proportion of OKM1+ cells remained unchanged after the inactivation process, the density of OKM1 on both K562-treated ECc and Ab-KLCL-treated ECc increased significantly. Morphologic analysis revealed no apparent differences in the percentages of LGL before and after treatment with K562 or Ab-KLCL. Finally, IL-2 restored lytic potential to both K562-treated ECc and Ab-KLCL-treated ECc and, in addition, IL-2-induced enhancement of Ab-KLCL-treated ECc was accompanied by a partial reexpression of Leu-11a. These data support the hypothesis that NK-cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity may result from a common lytic mechanism, although the initiation steps and regulation of the pathway are distinct.
Abrams
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SI
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46223.
Brahmi
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D000920:Antibody-Dependent Cell Cytotoxicity; D000954:Antigens, Surface / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D012397:Rosette Formation; D014407:Tumor Cells, Cultured / Q000276:immunology*
D000954:Antigens, Surface