scholarly journals Anti-Proliferative Effect of Allium senescens L. Extract in Human T-Cell Acute Lymphocytic Leukemia Cells

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 35
Author(s):  
Jiyeon Kim ◽  
Dae Han Lee ◽  
Bazarragchaa Badamtsetseg ◽  
Sangwoo Lee ◽  
Soon Ae Kim
Keyword(s):  
T Cell ◽  
Acute Lymphocytic Leukemia ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Combined Treatment ◽  
Lymphocytic Leukemia ◽  
Jurkat Cells ◽  
Ros Generation ◽  
Normal Peripheral Blood ◽  
Human T Cell

Allium species are well known plants distributed throughout the world, and they contain various bioactive components with different biological activities including anti-cancer effects. In this study, we investigated the inhibitory effect of Allium senescens L. (A.S.) extract on cell survival and IL-2-mediated inflammation in human T cell acute lymphocytic leukemia (T-ALL) Jurkat cells. Our results showed that A.S. extract induced caspase-dependent apoptosis of Jurkat cells with no significant cytotoxicity in the normal peripheral blood mononuclear cells. A.S. extract induced ROS generation through the activation of MAPK p38 phosphorylation. It also inhibited IL-2 mRNA expression and NF-κB signaling mediated by phorbol 12-myristate 13-acetate, and phytohemagglutinin. Combined treatment with A.S. extract and axitinib/dovitinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. These results provide novel information on the potential use of A.S. extract as a therapeutic herbal agent for the treatment and prevention of T-ALL.

scholarly journals Sizing of the human T cell receptor alpha locus and detection of a large deletion in the Molt-4 cell line

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1744-1747 ◽  
Author(s):  
MS Roth ◽  
FS Collins ◽  
D Ginsburg
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Cell Receptor ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Chain Gene ◽  
Normal Peripheral Blood ◽  
Receptor Alpha ◽  
Human T Cell ◽  
Cell Receptor Alpha

Abstract The human T cell receptor alpha (TCR-alpha) chain gene consists of discontinuous DNA segments encoding multiple variable (V), multiple joining (J), and one constant (C) region. Unlike other immunoglobulin or TCR genes, however, the TCR-alpha locus exhibits an unusual dispersal of J segments that occupy a region of greater than 50 kilobases (kb) upstream of the C region, with the exact size still unknown. We report here the study of the TCR-alpha genetic locus by using pulsed-field gel electrophoresis (PFGE), which permits the separation of large DNA fragments. Analysis of DNA prepared from normal peripheral blood mononuclear cells, human endothelial cells, and a B cell line demonstrates that both V and C sequences are contained within a single 400-kb SfiI restriction fragment. PFGE analysis of the T cell line Molt 4 suggests a greater than 600-kb deletion involving the TCR- alpha gene.

scholarly journals Comparative density of the human T-cell antigen T65 on normal peripheral blood T cells and chronic lymphocytic leukemia cells

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 657-662 ◽  
Author(s):  
SB Wormsley ◽  
ML Collins ◽  
I Royston
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Surface Density ◽  
Specific Antigen ◽  
Lymphocytic Leukemia ◽  
Normal Peripheral Blood ◽  
Human T Cell

Abstract A 65,000 dalton T-cell specific antigen previously demonstrated to be present on the surface of normal and malignant T cells, but not normal B cells, has been detected on the surface of leukemic cells from patients wih nonsecretory, surface immunoglobulin-positive chronic lymphocytic leukemia (CLL). By means of immunofluorescence and flow cytometry, the relative surface density of the T65 antigen on CLL cells was compared to that on normal peripheral blood T cells and human thymocytes, as well as cell lines of T-cell lineage. In all cases, the CLL cells had a more homogeneous and a lower median fluorescence intensity than that of normal circulating T cells. Thymocytes were composed of three populations, two with low surface density of T65 resembling the CLL cells and the other with higher density similar to normal T cells. The staining of cell lines varied from bright, heterogeneous staining (8402) to uniform, low-density staining (Molt- 4). The implications of these findings with regard to lymphocyte differentiation are discussed.

scholarly journals Comparative density of the human T-cell antigen T65 on normal peripheral blood T cells and chronic lymphocytic leukemia cells

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 657-662
Author(s):  
SB Wormsley ◽  
ML Collins ◽  
I Royston
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Surface Density ◽  
Specific Antigen ◽  
Lymphocytic Leukemia ◽  
Normal Peripheral Blood ◽  
Human T Cell

A 65,000 dalton T-cell specific antigen previously demonstrated to be present on the surface of normal and malignant T cells, but not normal B cells, has been detected on the surface of leukemic cells from patients wih nonsecretory, surface immunoglobulin-positive chronic lymphocytic leukemia (CLL). By means of immunofluorescence and flow cytometry, the relative surface density of the T65 antigen on CLL cells was compared to that on normal peripheral blood T cells and human thymocytes, as well as cell lines of T-cell lineage. In all cases, the CLL cells had a more homogeneous and a lower median fluorescence intensity than that of normal circulating T cells. Thymocytes were composed of three populations, two with low surface density of T65 resembling the CLL cells and the other with higher density similar to normal T cells. The staining of cell lines varied from bright, heterogeneous staining (8402) to uniform, low-density staining (Molt- 4). The implications of these findings with regard to lymphocyte differentiation are discussed.

scholarly journals Sizing of the human T cell receptor alpha locus and detection of a large deletion in the Molt-4 cell line

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1744-1747
Author(s):  
MS Roth ◽  
FS Collins ◽  
D Ginsburg
Keyword(s):  
T Cell ◽  
Cell Line ◽  
T Cell Receptor ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Chain Gene ◽  
Normal Peripheral Blood ◽  
Receptor Alpha ◽  
Human T Cell ◽  
Cell Receptor Alpha

The human T cell receptor alpha (TCR-alpha) chain gene consists of discontinuous DNA segments encoding multiple variable (V), multiple joining (J), and one constant (C) region. Unlike other immunoglobulin or TCR genes, however, the TCR-alpha locus exhibits an unusual dispersal of J segments that occupy a region of greater than 50 kilobases (kb) upstream of the C region, with the exact size still unknown. We report here the study of the TCR-alpha genetic locus by using pulsed-field gel electrophoresis (PFGE), which permits the separation of large DNA fragments. Analysis of DNA prepared from normal peripheral blood mononuclear cells, human endothelial cells, and a B cell line demonstrates that both V and C sequences are contained within a single 400-kb SfiI restriction fragment. PFGE analysis of the T cell line Molt 4 suggests a greater than 600-kb deletion involving the TCR- alpha gene.

scholarly journals Anticancer activities of bovine and human lactoferricin-derived peptides

2017 ◽  
Vol 95 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Mauricio Arias ◽  
Ashley L. Hilchie ◽  
Evan F. Haney ◽  
Jan G.M. Bolscher ◽  
M. Eric Hyndman ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Mononuclear Cells ◽  
Biological Activities ◽  
Cell Penetrating Peptides ◽  
Jurkat Cells ◽  
Mammalian Host ◽  
Anticancer Activities ◽  
Normal Peripheral Blood ◽  
Cell Penetrating

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly–Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

scholarly journals Phytochemical characterization and biological activities of Plectranthus barbatus Andrews

2022 ◽  
Vol 82 ◽  
Author(s):  
M. F. Cordeiro ◽  
T. R. S. Nunes ◽  
F. G. Bezerra ◽  
P. K. M. Damasco ◽  
W. A. V. Silva ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Trichophyton Rubrum ◽  
Biological Activities ◽  
Sandwich Elisa ◽  
Immunomodulatory Activity ◽  
Potential Candidate ◽  
Leaf Extracts ◽  
Healthy Human ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood

Abstract Plectranthus barbatus Andrews (Lamiaceae) is widely distributed in the world and has a range of popular therapeutic indications. This work aimed to evaluate the phytochemical characterization of two leaf extracts of P. barbatus, and their antimicrobial, antineoplastic and immunomodulatory potential. After collection, herborization and obtainment of the P. barbatus aqueous extract (PBA) and acetone:water 7:3 P. barbatus organic extract (PBO), the phytochemical characterization was performed by high-performance liquid chromatography (HPLC). The antimicrobial activity was performed to determine the minimum inhibitory concentration (MIC) against eight bacterial strains using the microdilution test and the fungus Trichophyton rubrum by disc diffusion assay and microdilution test. Cytotoxicity was assessed by MTT and trypan blue methods in normal peripheral blood mononuclear cells (PBMCs) at concentrations ranged between 0.1 to 100 µg.mL-1 and in neoplastic cell lines Toledo, K562, DU-145 and PANC-1 at 1, 10 and 100 µg.mL-1 . Immunomodulatory activity, was evaluated by sandwich ELISA of proinflammatory cytokines at BALB/c mice splenocytes cultures supernatant. Both extracts presented flavonoids, cinnamic derivatives, steroids and ellagic acid. PBO showed bacteriostatic activity against Acinetobacter baumannii (MIC = 250 µg.mL-1) clinical isolate and PBA fungistatic activity against Trichophyton rubrum (MIC = 800 µg.mL-1). The extracts did not exhibit toxicity to PBMCs and neoplastic cells (IC50 > 100 µg.mL-1). Additionally, PBO at 100 µg.mL-1 significantly inhibited IFN-γ and IL-17A cytokines (p = 0.03). Plectranthus barbatus is a potential candidate for therapeutic use due to its low toxicity in healthy human cells and exhibits biological activities of medical interest as bacteriostatic, fungistatic and immunomodulatory.

scholarly journals Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus

Blood ◽  
1996 ◽  
Vol 88 (8) ◽  
pp. 3004-3009 ◽  
Author(s):  
BA Pancake ◽  
EH Wassef ◽  
D Zucker-Franklin
Keyword(s):  
T Cell ◽  
Mycosis Fungoides ◽  
Mononuclear Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Structural Proteins ◽  
Infected Cell Line ◽  
Cutaneous T Cell Lymphoma ◽  
Serologic Tests ◽  
Human T Cell

Although most patients with the cutaneous T-cell lymphoma, mycosis fungoides (MF), are seronegative for human T-cell lymphotropic virus-I or -II (HTLV-I/II) when tested by assays that measure only antibodies to the viral structural proteins, the majority of such patients harbor HTLV-I-related pol and tax proviral sequences that encode proteins not included in routinely used serologic tests. Tax mRNA has also been detected in their peripheral blood mononuclear cells (PBMC). Therefore, it seemed possible that these patients have antibodies to the tax protein. To investigate this, enzyme-linked immunosorbent assays (ELI-SAs) and Western blot assays were set up, using as antigens the full-length HTLV-I tax cloned from the prototypic HTLV-I-infected cell line, C91PL, and from PBMC of a MF patient, as well as a synthetic peptide made to the carboxy-terminal 20 amino acids of tax-I. Of 60 MF patients whose PBMC were shown to be positive for tax proviral DNA and mRNA, 50 (83%) were shown to have tax antibodies. The antigen derived from the MF patient was most useful in detecting such antibodies. These results demonstrate the need for including other HTLV-related antigens in addition to gag and env in serologic tests used to identify HTLV-infected individuals. The findings underscore the fact that individuals considered seronegative on the basis of currently used tests can be infected with HTLV.

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