Defective natural killer cell activity of peripheral blood lymphocytes correlates with the degree of neutropenia in patients with chronic idiopathic neutropenia of adults.
Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and CD56+, but not CD57+, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages of perforin-expressing and granzyme B-expressing CD16+ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified.
Papadaki
H A
HA
Department of Hematology of the University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Coulocheri
S
S
Xylouri
I
I
Chatzivassili
A
A
Konsolas
J
J
Katrinakis
G
G
Karkavitsas
N
N
Eliopoulos
G D
GD
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007370:Interferon Type I / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D015703:Antigens, CD; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins