Natural Killer Cell Abnormalities Research Articles

Morphological variants of leukemic cells in B chronic lymphocytic leukemia are associated with different T cell and NK cell abnormalities.

B chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease. The different morphological variants of leukemic B cells appear to define different clinical groups of patients. Several abnormalities have been found in T lymphocytes and natural killer (NK) cells from B-CLL patients. We have investigated the phenotypic and functional characteristics of purified CD2+ cells from B-CLL patients at Binet's stage A and classified according to the neoplastic B lymphocyte morphology criteria: 32 patients with typical B-CLL and 12 patients with atypical B-CLL. Forty-three age and sex matched healthy controls were also studied. In fresh purified CD2+ cells from typical B-CLL patients, percentages of CD4+, CD4+CD45RA+, CD8+CD45RA+ T lymphocytes and CD3-CD56+ (NK) cells were significantly higher than those found in atypical B-CLL patients. However, in DC2+ cells from typical B-CLL patients, percentages of CD3+, CD3+DR+, CD8+, CD4+CD45RO+, and CD3+CD56+ cells were significantly lower than those found in atypical B-CLL patients. Increased percentage of NK cells was only found in typical B-CLL patients. The proliferative response and the production of interleukin (IL)-2 and IL-4 by phytohemagglutinin (PHA) stimulated CD2+ cells were significantly higher in typical B-CLL patients than in atypical B-CLL patients. We concluded that different patterns of phenotypic and functional alterations in the T lymphocytes and NK cells of B-CLL patients are found in patients with typical or atypical B-CLL defined according to the morphology of the leukemic cells.

Functional abnormalities of natural killer cells in childhood hemophagocytic syndrome

To analyze the abnormality of natural killer (NK) cells in childhood hemophagocytic syndrome (HPS), we investigated the numbers, cytolytic functions of circulating NK cells, and responsiveness to cytokines by flow cytometry, 51Cr-releasing and single-cell assay in 13 patients. In the active phase, the relative number of CD 16+ cells was decreased in 3 patients. NK activity was depressed in 6 patients but normal in the remaining 7 in the active phase. Lymphokine-activated killer (LAK) activity showed the similar tendency. The responsiveness of NK cells to IFN-gamma was absent, but that to IL-2 was normal in the active phase. Single-cell assay showed depressed maximal recycling capacity (MRC) and killing capacity values in the active phase and in remission phase, respectively. From these results, NK cells have such functional abnormalities as the absence of responsiveness to IFN-gamma and depressed recycling capacity in the active phase of childhood HPS. Further, abnormality of killing capacity of NK cells may exist even in the remission phase.

Lymphokine and NK Cell Activity in Sickle Cell Disease

Patients with childhood sickle cell disease (SCD) had in vitro interferon alpha (IFN-α) and gamma (IFN-γ), lymphotoxin (LT) expression, and natural killer (NK) cell function measured. The corresponding measurements were also made for age-matched and gender-matched controls. IFN-α in both patient groups and in controls appeared normal, IFN-γ was decreased compared to matched controls independent of patient group status, and the assessment of LT activity demonstrated equal abnormal and normal results. In vitro NK cell lytic function in SCD was approximately 50% that of the controls. We conclude that combined IFN-γ and NK cell abnormalities result in heightened risk for sickle cell morbidity.

Natural killer cells in common variable immunodeficiency and selective IgA deficiency

Natural killer (NK) cell activity was found to be above normal levels in patients with common variable immunodeficiency (CVID), whereas no NK cell abnormality was found in patients with selective IgA deficiency. The lytic activity of a given amount of peripheral blood lymphocytes was about five times higher in CVID patients than in controls when either K562, Molt 4, or Chang cells were used as targets. Interferon boosted the activity in patients and controls to about the same degree. NK activity was positively correlated to the number of circulating T8 + cells. Dysfunction of T cells, increase in suppressor cell function, and hyperactivity of NK cells in CVID may have a common background, possibly an abnormality related to interferon production.