N-acetylcysteine mildly inhibits the graft-vs.-leukemia effect but not the lymphokine activated cells (LAK) activity

2007 ◽  
Vol 17 (3) ◽  
pp. 198-202 ◽  
Author(s):  
Lola Weiss ◽  
Shoshana Reich ◽  
Michael Zeira ◽  
Reuven Or ◽  
Igor B. Resnick ◽  
...  
Keyword(s):  
Lak Activity

scholarly journals Low molecular weight B-cell growth factor and recombinant interleukin-2 are together able to generate cytotoxic T lymphocytes with LAK activity from the bone marrow cells of children with acute lymphoblastic leukemia

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1355-1359 ◽  
Author(s):  
MX Zhou ◽  
HW Jr Findley ◽  
AH Ragab
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Growth Factor ◽  
Cytotoxic T Lymphocytes ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Recombinant Interleukin 2 ◽  
B Cell Growth Factor ◽  
Lak Activity

Abstract We are reporting here that low-mol wt B-cell growth factor (LMW-BCGF) and recombinant interleukin-2 (rIL-2) are together able to induce CD3+ cytotoxic T lymphocytes (CTL) with lymphokine-activated killer cell (LAK) activity from the bone marrow (BM) cells of children with acute lymphoblastic leukemia (ALL). Ficoll-Hypaque (FH)-separated BM cells were obtained from patients with active disease (at diagnosis N = 13, in relapse N = 15) and in complete remission (CR; N = 12). CD3+ cells were removed by Leu-4 antibody and immunobeads. Cells were cultured (10(5) cells/mL) in semisolid media with rIL-2 (100 mu/mL), LMW-BCGF (0.1 mu/mL), and the combination of rIL-2 plus LMW-BCGF, respectively, for seven to ten days. Pooled colonies were harvested for phenotyping. LMW-BCGF plus rIL-2 induced large numbers of CD3+ colonies from CD3- precursors. rIL-2 alone did not induce colony formation. In addition, cells were cultured in liquid media with LMW-BCGF, rIL-2, and the combination of LMW-BCGF plus rIL-2, respectively, for seven to 21 days. They were harvested for phenotyping, and cytotoxicity assays were performed v K562, Raji, and autologous leukemic cells. LMW-BCGF plus rIL-2 induced significant expansion of CD3+ cells from CD3- precursors, and these cells were activated to kill autologous leukemic cells in addition to Raji and K562 cell lines. LMW-BCGF or rIL-2 alone did not induce significant expansion or activation of cytotoxic CD3- cells. Our hypothesis is that LMW-BCGF plus rIL-2 stimulates the proliferation and activation of CD3- precursors from the BM cells of children with acute leukemia to become CD3+ cells that have LAK activity. This finding may have therapeutic implications.

scholarly journals Increased LAK activity against HIV-infected cell lines in HIV-1+ individuals

2008 ◽  
Vol 89 (3) ◽  
pp. 356-361 ◽  
Author(s):  
C. GRYLLIS ◽  
M. A. WAINBERG ◽  
Z. BENTWICH ◽  
M. GORNITSKY ◽  
B. G. BRENNER
Keyword(s):  
Infected Cell ◽  
Cell Lines ◽  
Hiv 1 ◽  
Lak Activity

scholarly journals Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2335-2342 ◽  
Author(s):  
DJ Gottlieb ◽  
HG Prentice ◽  
HE Heslop ◽  
C Bello-Fernandez ◽  
AC Bianchi ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Killer Cell ◽  
Interleukin 2 ◽  
High Dose ◽  
Allogeneic Bone ◽  
Major Histocompatibility ◽  
Cell Numbers ◽  
Lak Activity

Abstract Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.

Combined effect of interleukin 2 and prolactin on generation of LAK activity by NK cells

Cytokine ◽  
1991 ◽  
Vol 3 (5) ◽  
pp. 464
Author(s):  
L. Matera ◽  
G. Bellone ◽  
A. Cesano ◽  
E. Oberholtzer
Keyword(s):  
Nk Cells ◽  
Interleukin 2 ◽  
Combined Effect ◽  
Lak Activity

N-Acetylcysteine Mildly Inhibits the Graft vs Leukemia Effect but Not the Lymphokine Activated Cells (LAK) Activity.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5171-5171
Author(s):  
Michael Y. Shapira ◽  
Lola Weiss ◽  
Shoshana Reich ◽  
Michael Zeira ◽  
Shimon Slavin
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Tumor Cell Line ◽  
Control Group ◽  
Murine Models ◽  
Spleen Cells ◽  
Idiopathic Pneumonia Syndrome ◽  
Graft Vs Host Disease ◽  
Negative Effect ◽  
Lak Activity

Abstract N-acetylcysteine (NAC) is a known antioxidant and induces modulation of glutathione cellular content effects. It has been suggested that in the context of stem cell transplantation (SCT), NAC was suggested as a possible agent in order to prevent and treat graft-vs.-host disease, veno-occlusive disease and idiopathic pneumonia syndrome. We investigated the possible effect of NAC on graft-vs.-leukemia effect (GVL) and lymphokine activated cells (LAK) activity in murine models. After 10 days of either oral or intraperitoneal NAC treatment, the cytotoxic activity of the LAK cells against Yac cells (H-2a, NK sensitive tumor cell line)did not significantly differ from LAK activity generated from spleen cells obtained from untreated controls. However, NAC mildly suppressed GVL (appearance of BCL1 leukemia in 8/36 animals treated with NAC as compared to 0/20 in the transplantation control group, p=0.023, figure 1). In spite of this mild suppression of GVL, no negative effect on engraftment, judged by achievement of donor chimerism, was seen. We conclude that NAC usage in SCT maybe relatively safe in regard to the GVL effect, yet further clinical studies are warranted. Figure Figure

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