Decreased natural killer (NK) cell function in chronic NK cell lymphocytosis associated with decreased surface expression of CD11b.
Chronic natural killer cell lymphocytosis (CNKL) is characterized by greatly increased numbers of natural killer (NK) cells and patients with this disease may survive for long periods. This is in contrast to patients with leukemic proliferations of NK cells who can have a rapidly progressive clinical course. We identified a pediatric patient who was largely healthy who had CNKL and we sought to determine if the expanded CD16(+)CD3(-) population in this patient functions differently than classical NK cells. Cytotoxic activity against NK cell-sensitive K562 target cells was present, but lower than that in control donors when calculated as lytic units per CD16(+)CD3(-) cell. This cytolytic activity was inducible in patient samples by IL-2/IL-12 stimulation proportionately to that induced in samples from control donors. Intracellular perforin was also present and induced in patient CD16(+)CD3(-) cells similarly to controls. Other presumed NK cell activities, such as IL-2/IL-12 induced IFN-gamma expression and initiation of apoptosis evidenced by annexin V binding after CD16 crosslinking were present in patient samples. Patient CD16(+)CD3(-) cells, however, differed from classical NK cells, as the majority did not express CD56, CD57, CD8, or CD11b. Most convincingly, there was a 5 log decrease in CD11b expression in patient CD16(+)CD3(-) cells compared to control as determined by mean channel fluorescence. These observed differences may explain the relatively benign phenotype of this disorder.
Orange
J S
JS
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Chehimi
J
J
Ghavimi
D
D
Campbell
D
D
Sullivan
K E
KE
D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D002648:Child; D002908:Chronic Disease; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D008218:Lymphocytosis / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000032:analysis*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG / Q000032:analysis
D017252:CD3 Complex; D019002:CD56 Antigen; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG; D054353:Perforin; D007371:Interferon-gamma