scholarly journals Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1355-1360 ◽  
Author(s):  
F Santiago-Schwarz ◽  
C Panagiotopoulos ◽  
A Sawitsky ◽  
KR Rai
Keyword(s):  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Lymphocytic Leukemia ◽  
Lak Cell ◽  
Cell Chronic Lymphocytic Leukemia

Abstract We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B- CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B- cell growth and/or growth stimulation of the leukemic clone in B-CLL.

scholarly journals Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1355-1360
Author(s):  
F Santiago-Schwarz ◽  
C Panagiotopoulos ◽  
A Sawitsky ◽  
KR Rai
Keyword(s):  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Lymphocytic Leukemia ◽  
Lak Cell ◽  
Cell Chronic Lymphocytic Leukemia

We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B- CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B- cell growth and/or growth stimulation of the leukemic clone in B-CLL.

scholarly journals Antigen presentation in an HLA-DR-restricted fashion by B-cell chronic lymphocytic leukemia cells

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 102-108 ◽  
Author(s):  
M Yasukawa ◽  
T Shiroguchi ◽  
A Inatsuki ◽  
Y Kobayashi
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Antigen Presentation ◽  
Interleukin 2 ◽  
Class Ii ◽  
Hla Class Ii ◽  
Lymphocytic Leukemia ◽  
Hla Dr ◽  
Cell Chronic Lymphocytic Leukemia

The ability of B-cell chronic lymphocytic leukemia (B-CLL) cells to present antigen to antigen-specific T cells was investigated. B-CLL cells present herpes simplex virus (HSV) antigen and purified protein derivative (PPD) to HSV- and PPD-specific, interleukin-2-dependent T- cell lines in an antigen-specific manner. Treatment of B-CLL cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced markedly increased levels of HLA-DR expression. TPA-treated B-CLL cells showed substantially more effective presentation, especially at low antigen concentrations, than did untreated B-CLL cells. By coculturing different allogeneic combinations of B-CLL cells and T cells and by adding anti-HLA-DR monoclonal antibody to cultures, it was found that antigen presentation by B-CLL cells was restricted by HLA-DR in the same way as for macrophages. We concluded from these experiments that B- CLL cells have a capacity to serve as antigen-presenting cells in an HLA class II-restricted fashion and that increasing the amount of HLA class II antigen and activation of B-CLL cells resulted in effective antigen presentation.

scholarly journals The proliferative response of B cell chronic lymphocytic leukemia to interleukin 2: functional characterization of the interleukin 2 membrane receptors

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1667-1673 ◽  
Author(s):  
I Touw ◽  
L Dorssers ◽  
B Lowenberg
Keyword(s):  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Functional Characterization ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Membrane Receptors ◽  
Thymidine Uptake ◽  
Cell Chronic Lymphocytic Leukemia

Abstract To determine the growth properties of B cell chronic lymphocytic leukemia (B CLL) and to identify possible abnormalities thereof, we examined the in vitro action of interleukin 2 (IL2) in four patients. Using radiolabeled IL2 and monoclonal antibodies reactive with IL2 membrane receptors we show that CLL cells, after their activation in vitro, express IL2 receptors of a high- as well as a low-affinity type, exactly as has been reported for normal T and B blasts. In three of the four reported cases, CLL proliferation (measured with 3H-thymidine incorporation) depended on the addition of phytohemagglutinin (PHA) to activate the cells and IL2 (optimal concentration, 10 to 100 U IL2/mL). In contrast, the cells of the fourth case of CLL (CLL-4) proliferated in an autonomous fashion, ie, without a need for PHA and IL2 in culture. Specific blocking of the IL2-binding sites with anti-IL2 receptor monoclonal antibodies almost completely inhibited the proliferation of these cells, which indicated that functional IL2 receptors were required for the autonomous proliferation. The demonstration of low concentrations of IL2 activity in the culture medium conditioned by the cells suggests that endogenous IL2 had been responsible for the spontaneous 3H-thymidine uptake by the CLL cells of patient 4. However, we were unable to extract IL2 mRNA from the cells (neither fresh nor after various in vitro incubations) in quantities detectable by Northern blot analysis that would prove that the CLL cells of patient 4 were actively synthesizing IL2 during culture. Thus, individual cases of B CLL are subject to variable growth regulation involving functional IL2 receptors on the cell surface: after activation with PHA the cells respond to exogenous IL2 in a fashion similar to normal B lymphocytes, or the cells are stimulated by endogenous IL2 (or an IL2-like activity) and do not require activation with PHA.

scholarly journals Interleukin 2 production in B cell chronic lymphocytic leukemia

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 840-847 ◽  
Author(s):  
JF Rossi ◽  
B Klein ◽  
T Commes ◽  
M Jourdan
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Interleukin 2 (IL 2) production by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was investigated in 22 patients with active untreated B cell chronic lymphocytic leukemia (B- CLL) and in 15 healthy donors. PBMCs from healthy donors demonstrated an IL 2 synthesis of 12.4 +/- 10 U/mL. B-CLL PBMCs produced a significant amount of IL 2 (8 +/- 6.6 U/mL) despite the low percentage of T cells (13% +/- 8%) associated with this disease compared with that found in healthy donors (63% +/- 7.5%). If IL 2 production is expressed as units per milliliter per 10(4) T cells, its level in patients with B- CLL (1.1 U/mL/10(4) T cells) is five times greater than that of the controls (0.19 units). When expressed as units per milliliter per liter of blood, the B-CLL patients produce approximately 12 times as much IL 2 as controls. IL 2 production in normal controls was doubled after irradiation of PBMCs or addition of indomethacin. This increase was not seen with B-CLL PBMCs suggesting that the latter have been devoid of prostaglandin-producing normal IL 2 suppressor cells. By mixing normal or B-CLL T cells with non-T cells we found that T cells from patients with B-CLL stimulated by normal accessory cells produced the same amount of IL 2 as normal T cells. Moreover, B-CLL non-T cells (mainly B leukemic cells) produced no IL 2 themselves but played a much more efficient role in IL 2 production than did non-T cells from healthy donors. This was not due to detectable IL 1 production by these cells. The IL 2 produced by B-CLL PBMCs was partially purified and recovered in a 16,000 mol wt fraction, the same mol wt as IL 2 from normal cells.

CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2146-2155 ◽  
Author(s):  
Silvia Deaglio ◽  
Andrea Capobianco ◽  
Luciana Bergui ◽  
Jan Dürig ◽  
Fortunato Morabito ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Membrane Lipid ◽  
Lymphocytic Leukemia ◽  
Specific Expression ◽  
Cellular Models ◽  
Richter Syndrome ◽  
Cell Chronic Lymphocytic Leukemia

Abstract The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CLL cells. Indeed, mAb ligation is followed by Ca2+ fluxes and by a markedly increased proliferation. The unsuitability of CD38 to perform as a receptor is obviated through close interaction with the B-cell–receptor (BCR) complex and CD19. On mAb binding, CD38 translocates to the membrane lipid microdomains, as shown by a colocalization with the GM1 ganglioside and with CD81, a raft-resident protein. Finally, CD38 signaling in IL-2–treated B-CLL cells prolonged survival and induced the appearance of plasmablasts, providing a pathogenetic hypothesis for the occurrence of Richter syndrome.

scholarly journals Responses to Human CD40 Ligand/Human Interleukin-2 Autologous Cell Vaccine in Patients with B-Cell Chronic Lymphocytic Leukemia

2005 ◽  
Vol 11 (19) ◽  
pp. 6916-6923 ◽  
Author(s):  
Ettore Biagi ◽  
Raphael Rousseau ◽  
Eric Yvon ◽  
Mary Schwartz ◽  
Gianpietro Dotti ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Interleukin 2 ◽  
Cd40 Ligand ◽  
Lymphocytic Leukemia ◽  
Cell Vaccine ◽  
Autologous Cell ◽  
Cell Chronic Lymphocytic Leukemia

Serum Levels of CD8 Antigen and Soluble Interleukin 2 Receptors in Patients with B Cell Chronic Lymphocytic Leukemia

1991 ◽  
Vol 85 (2) ◽  
pp. 57-61 ◽  
Author(s):  
Caterina Musolino ◽  
Enrico Di Cesare ◽  
Andrea Alonci ◽  
Alessandro Allegra ◽  
Annunziata Orlando ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Lymphocytic Leukemia ◽  
Cd8 Antigen ◽  
Cell Chronic Lymphocytic Leukemia

scholarly journals Antigen presentation in an HLA-DR-restricted fashion by B-cell chronic lymphocytic leukemia cells

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 102-108
Author(s):  
M Yasukawa ◽  
T Shiroguchi ◽  
A Inatsuki ◽  
Y Kobayashi
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Antigen Presentation ◽  
Interleukin 2 ◽  
Class Ii ◽  
Hla Class Ii ◽  
Lymphocytic Leukemia ◽  
Hla Dr ◽  
Cell Chronic Lymphocytic Leukemia

Abstract The ability of B-cell chronic lymphocytic leukemia (B-CLL) cells to present antigen to antigen-specific T cells was investigated. B-CLL cells present herpes simplex virus (HSV) antigen and purified protein derivative (PPD) to HSV- and PPD-specific, interleukin-2-dependent T- cell lines in an antigen-specific manner. Treatment of B-CLL cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced markedly increased levels of HLA-DR expression. TPA-treated B-CLL cells showed substantially more effective presentation, especially at low antigen concentrations, than did untreated B-CLL cells. By coculturing different allogeneic combinations of B-CLL cells and T cells and by adding anti-HLA-DR monoclonal antibody to cultures, it was found that antigen presentation by B-CLL cells was restricted by HLA-DR in the same way as for macrophages. We concluded from these experiments that B- CLL cells have a capacity to serve as antigen-presenting cells in an HLA class II-restricted fashion and that increasing the amount of HLA class II antigen and activation of B-CLL cells resulted in effective antigen presentation.

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