Anti-myeloma activity of natural killer lymphocytes.
Natural killer (NK) cells are assumed to contribute to a graft-versus-leukaemia effect. In vitro experiments have shown that many leukaemic cells are NK-cell sensitive. Nevertheless, no data concerning the influence of purified NK cells on malignant myeloma (MM) cells exist. We co-incubated NK cells with three different MM cell lines and fresh bone marrow samples of nine MM patients. The proportion of vital MM cells was determined before and after co-cultivation by a flow-cytometry-based assay. All MM cells tested, with the exception of one cell line (NCI H929), were susceptible to a NK-cell attack even without exogenous interleukin 2 (IL-2). The mean killing of the native MM samples was 23.1 +/- 5.4% and 34.5 +/- 6.5% at 10:1 and 20:1 effector:target ratio respectively, This corresponded to about 2/3 of those values obtained with the highly sensitive line K562. In contrast, CD34-positive haematopoietic stem cells as well as peripheral mononuclear cells were completely resistant under similar experimental conditions (1.3% killing). To elucidate the underlying triggering mechanisms, we measured human leucocyte antigen (HLA)-class I expression of the MM cells. No evidence for HLA loss, which could have explained the NK-cell recognition if it occurred, was demonstrated. These findings may contribute to the understanding of in vivo NK-cell activation and encourage clinical applications of NK cells for MM patients.
Frohn
Christoph
C
Institute of Immunology and Transfusion Medicine, University of Lübeck, Lübeck, Germany.
Höppner
Maike
M
Schlenke
Peter
P
Kirchner
Holger
H
Koritke
Petra
P
Luhm
Jürgen
J
D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D014407:Tumor Cells, Cultured