scholarly journals Functional interleukin-2 receptors are expressed on natural killer-like leukemic cells from a dog with cutaneous lymphoma

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 636-645 ◽  
Author(s):  
SC Helfand ◽  
JF Modiano ◽  
PF Moore ◽  
SA Soergel ◽  
PS MacWilliams ◽  
...  

We identified a dog with large granular lymphocytic leukemia and cutaneous lymphoma that exhibited constitutive expression of interleukin-2 (IL-2) receptors by the leukemic peripheral blood lymphocytes. The leukemic cells phenotypically resembled natural killer (NK) cells, and their surface IL-2 receptors were functional, as determined by the capacity to bind human recombinant IL-2 with high- affinity resulting in the transduction of proliferation signals and in the development of lymphokine-activated killer cell activity. These cells produced IL-2 spontaneously, and they may have maintained their proliferative state through an IL-2-dependent autocrine growth pathway. Our results indicate that neoplastic lymphocytes of syndromes that involve circulating leukemic cells with dermotropism can originate from NK-like cells. Additionally, the data also suggest that proliferative conditions such as these may be the result of the aberrant production of IL-2. Further, this case illustrates the potential for the use of hematopoietic malignancies in the dog as a suitable animal model for immune targeting of IL-2 receptors as a novel treatment approach for similar malignancies of human beings.

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.


Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  

Abstract Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.


2019 ◽  
Vol 5 (10) ◽  
pp. FSO425
Author(s):  
Ricardo García-Muñoz ◽  
María-Josefa Nájera ◽  
Jesús Feliu ◽  
Judith Antón-Remírez ◽  
Enrique Ramalle-Gómara ◽  
...  

Aim: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. Patients & methods: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. Results: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. Conclusion: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.


1996 ◽  
Vol 37 (5) ◽  
pp. 445-450 ◽  
Author(s):  
L. E. Robertson ◽  
A. W. Denny ◽  
Y. O. Huh ◽  
W. Plunkett ◽  
M. J. Keating ◽  
...  

2006 ◽  
Vol 31 (5) ◽  
pp. 588-596 ◽  
Author(s):  
Christopher M. Sellar ◽  
Daniel G. Syrotuik ◽  
Catherine J. Field ◽  
Gordon J. Bell

To determine the effect of carbohydrate supplementation on the immune and stress hormone responses to 1 h of strenuous rowing exercise, 22 male subjects were randomly assigned to a placebo (PLA, n = 11) or carbohydrate (CHO, n = 11) group. Subjects completed 3 d of modified dietary intake, a standardized pre-exercise meal, and consumed either a carbohydrate beverage (1 g·kg body mass–1) or a non-caloric placebo drink before, during, and after a 1 h rowing trial. Increases were observed in adrenocorticotrophic hormone, cortisol, blood leukocytes, neutrophils, and natural killer cell concentrations and activity, whereas the ability of peripheral blood monouclear cells (PBMCs) to respond (interleukin-2 (IL-2) production) to stimulation was reduced 5 min after exercise in both groups (p < 0.05). Lymphocytes were also elevated, but in the PLA group only (p < 0.05). One hour after exercise, blood leukocytes remained elevated owing to increased neutrophil concentrations, whereas a number of lymphocyte subsets (CD3+, CD3+/4+, CD3+/8+, CD20+, CD25+, CD4+/25+, CD8+/25+) and the ability of PBMCs to respond to stimulation (IL-2, interferon-γ (IFN-γ) production) were lower than resting values in both groups (p < 0.05). Carbohydrate supplementation to athletes in the post-prandial state undergoing a 1 h rowing trial resulted in attenuation of the post-exercise increase in peripheral blood lymphocyte concentration, but had little effect on the ability of PBMCs to produce cytokines following stimulation, natural killer cell activity, stress hormone concentrations, exercise performance, or self-reported incidence of illness during the 14 d period following the experimental trial.


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