title: Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia.
abstract: Natural killer (NK) cell activity is severely impaired in untreated patients with hairy cell leukemia (HCL). In an attempt to investigate whether this impairment is related to a defect at the target cell binding and/or at the post target cell binding level, we evaluated the peripheral blood mononuclear cells (PBMC) of HCL patients for their ability to: (1) bind and kill K-562 NK-sensitive targets at the single cell binding level; (2) release the NK cytotoxic factor (NKCF) under different in vitro stimuli, including K-562 and phytohemoagglutinin; and (3) kill K-562 targets in a lectin-dependent cellular cytoxicity (LDCC) assay. This study demonstrates that untreated HCL patients' PBMC show a low ability to form conjugates with K-562 targets at the single cell binding level (5.7% +/- 1.0%) with respect to patients studied after treatment (9.3% +/- 1.3%) and controls (15.0% +/- 4.0%); P less than .05 and P less than .001, respectively. A decreased ability to kill the bound target was demonstrated in untreated cases (1.2% +/- 1.1%) versus patients studied after treatment and controls (12.3% +/- 1.6%, 17.0% +/- 3.1% respectively); P less than .001 in both conditions. After activation of effector cells with interleukin-2 (IL-2) in vitro, an increase in the ability of PBMC to form conjugates with K-562 targets and kill the bound target was demonstrated in each group of patients. Moreover, IL-2 was able to increase the cytotoxicity against NK-sensitive targets in all patients tested. Evaluation of NKCF production showed that untreated patients release low levels of NKCF when PBMC were incubated in the presence of K-562 stimulators (1.8% +/- 0.7%) with respect to patients after interferon-alpha (IFN-alpha) therapy (7.6% +/- 2.1%) and controls (12.9% +/- 2.2%); P less than .02 and P less than .001, respectively. When the recognition mechanisms were bypassed by triggering the cells with lectins in an LDCC assay, we demonstrated an increase of the lytic activity in both groups of patients with respect to the baseline values. However, the cytotoxic capacity observed in untreated patients was significantly lower than that observed in subjects after IFN-alpha therapy and controls (P less than .001). These findings suggest that the impaired NK activity observed in patients with HCL is related to defects both at the target and posttarget cell binding levels.
authors.affiliation: Padua University School of Medicine, Department of Clinical Medicine, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.forename: R
authors.initials: R
authors.lastname: Zambello
authors.forename: C
authors.initials: C
authors.lastname: Agostini
authors.forename: A
authors.initials: A
authors.lastname: Ambrosetti
authors.forename: T
authors.initials: T
authors.lastname: Chisesi
authors.forename: R
authors.initials: R
authors.lastname: Raimondi
authors.forename: P
authors.initials: P
authors.lastname: Bulian
authors.forename: G
authors.initials: G
authors.lastname: Pizzolo
authors.forename: G
authors.initials: G
authors.lastname: Semenzato
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D055646:Killer Factors, Yeast; D007700:Kinetics; D037102:Lectins; D007943:Leukemia, Hairy Cell / Q000276:immunology* / Q000628:therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011506:Proteins / Q000032:analysis; D011994:Recombinant Proteins; D012016:Reference Values
chemical_list: D015703:Antigens, CD; D007370:Interferon Type I; D055646:Killer Factors, Yeast; D037102:Lectins; D011506:Proteins; D011994:Recombinant Proteins