Inhibition of lymphocyte responsiveness by a glial tumor cell-derived suppressive factor

1987 ◽  
Vol 67 (6) ◽  
pp. 874-879 ◽  
Author(s):  
Thomas L. Roszman ◽  
William H. Brooks ◽  
Lucinda H. Elliott
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Human Peripheral Blood ◽  
Calf Serum ◽  
Lymphocyte Activation ◽  
Peripheral Blood Lymphocytes ◽  
Prostaglandin E ◽  
Suppressive Activity ◽  
Glial Tumor ◽  
Culture Supernatants

✓ The results of this study demonstrate the presence of suppressive factor(s) in the tissue culture supernatants of cloned and freshly explanted malignant glioma cells. Culture supernatants obtained from these glial cell lines were demonstrated to have potent suppressive activity as evidenced by their ability to inhibit the proliferative response of normal human peripheral blood lymphocytes induced by phytohemagglutinin and anti-OKT3 monoclonal antibodies. The results further demonstrate the existence of a dose-response relationship between these supernatants and inhibition of mitogen-induced lymphocyte activation. Maximum production of suppressive activity by glial tumor cells was dependent on: 1) the number of tumor cells seeded in culture, 2) whether fetal calf serum was present, and 3) the duration of culture. The production of the suppressive factor(s) was not inhibited by the addition of inhibitors of prostaglandin E synthesis. Experiments designed to determine at what time during lymphocyte activation the suppressive factor was most effective demonstrated that the culture supernatants must be added during the first 24 hours of culture to exhibit inhibitory properties. Finally, proliferation of both the T-helper and T-suppressor/cytotoxic subsets was equally well inhibited by the glial tumor cell culture supernatants.

scholarly journals THE EFFECT OF BORDETELLA PERTUSSIS ON LYMPHOCYTE CYCLIC AMP METABOLISM

1973 ◽  
Vol 137 (4) ◽  
pp. 1078-1090 ◽  
Author(s):  
Charles W. Parker ◽  
Stephen I. Morse
Keyword(s):  
Cyclic Amp ◽  
Bordetella Pertussis ◽  
Inhibitory Activity ◽  
Human Peripheral Blood ◽  
Biological Effects ◽  
Lymphocyte Activation ◽  
Culture Fluid ◽  
Peripheral Blood Lymphocytes ◽  
Prostaglandin E ◽  
Adrenergic Blockade

Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic ß adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism. Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE1), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37°C, the responses to all three agents were markedly inhibited. Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE1 and methacholine responses were also inhibited suggests that blockade at the level of the ß adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2–1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml. The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities. The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.

scholarly journals Innate Immunity Protein Tag7 Induces 3 Distinct Populations of Cytotoxic Cells That Use Different Mechanisms to Exhibit Their Antitumor Activity on Human Leukocyte Antigen-Deficient Cancer Cells

2017 ◽  
Vol 9 (6) ◽  
pp. 598-608 ◽  
Author(s):  
Tatiana N. Sharapova ◽  
Olga K. Ivanova ◽  
Natalia V. Soshnikova ◽  
Elena A. Romanova ◽  
Lidia P. Sashchenko ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
T Lymphocytes ◽  
Human Leukocyte Antigen ◽  
Tumor Cells ◽  
Human Peripheral Blood ◽  
Human Leukocyte ◽  
Peripheral Blood Lymphocytes ◽  
Immunity Protein ◽  
Leukocyte Antigen

The search for new immune response mechanisms capable of controlling immune-evasive tumor cells devoid of the MHC antigen is a challenging task for immunologists. In this study, we found that the treatment of human peripheral blood lymphocytes with the innate immunity protein Tag7 (PGRP-S, PGLYRP1) induces differentiation of the populations of NK (natural killer) cells and CD8+ and CD4+ T lymphocytes that are cytotoxic for human leukocyte antigen-negative tumor cells. These populations employ different mechanisms of tumor cell lysis (based on the release of granzymes in the case of NK cells and on the FasL-Fas interaction in the case of CD8+ and CD4+ T lymphocytes) and induce different death pathways (apoptosis or necroptosis) in tumor cells. An analysis of genes activated in leukocyte populations after Tag7 treatment and experiments with specific inhibitors have shown that the TREM-1 receptor expressed on the monocyte cell surface is essential for activation of cytotoxic activity. Overall, the results of this study provide evidence for a novel role of the Tag7 protein in the immune response.

scholarly journals C-reactive protein is produced by a small number of normal human peripheral blood lymphocytes.

1986 ◽  
Vol 164 (1) ◽  
pp. 321-326 ◽  
Author(s):  
A E Kuta ◽  
L L Baum
Keyword(s):  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocyte Culture ◽  
Nk Activity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Normal Human ◽  
Normal Human Peripheral Blood ◽  
Culture Supernatants ◽  
And Staphylococcus Aureus

Biosynthetic labeling with [35S]met and immunoprecipitation with anti-C-reactive protein (CRP) antibodies and Staphylococcus aureus indicate that cell surface CRP is produced by lymphocytes. The ability of anti-CRP to reduce NK activity, and the demonstration that 125I-anti-CRP-labeled PBL are found in low-density Percoll fractions associated with large granular lymphocyte (LGL) and NK activity suggest that S-CRP-bearing cells are NK effectors. The production of S-CRP by LGL supports this hypothesis. While lymphocytes were shown to synthesize S-CRP, monocytes produced no detectable S-CRP. The lymphocytes that produce S-CRP apparently do not secrete it; when lymphocyte culture supernatants were tested, no S-CRP was found. This is the first description of extrahepatic synthesis of CRP.

scholarly journals Growth-inhibitory activity of lymphoid cell plasma membranes. I. Inhibition of lymphocyte and lymphoid tumor cell growth.

1984 ◽  
Vol 99 (4) ◽  
pp. 1221-1226 ◽  
Author(s):  
K C Stallcup ◽  
A Dawson ◽  
M F Mescher
Keyword(s):  
Plasma Membrane ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Tumor Cells ◽  
Inhibitory Activity ◽  
Calf Serum ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Lymphoid Tumor ◽  
Normal Spleen

Membranes isolated from normal spleen cells or lymphoid tumor cells were found to inhibit in vitro growth of several murine tumor cell lines including a B cell hybridoma, a thymoma, and a mastocytoma. 50% inhibition occurred at membrane protein concentrations of 60-100 micrograms/ml. A similar concentration dependence was found for inhibition of [3H]-thymidine incorporation by tumor cells and for the lipopolysaccharide-induced mitogenic response of normal spleen cells. The inhibitory activity co-purified with the plasma membrane upon fractionation of crude membranes. Membrane solubilization with deoxycholate followed by dialysis to remove the detergent gave good recovery of inhibitory activity in the resulting reconstituted membranes. Membrane-mediated growth inhibition resulted from a decreased rate of proliferation and not from increased cell death. A toxic effect of the membranes was further ruled out by the finding that increasing the fetal calf serum content of the medium could substantially reverse the growth inhibition. Thus, the plasma membrane of lymphoid cells contains a component that can slow or stop the growth of cells in culture. This membrane component may have a role in cell contact-mediated regulation of growth.

The Direct Cytotoxicity of Activated Human Umbilical Cord Blood Dendritic Cells to Tumor Cell.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3812-3812
Author(s):  
Shi Jun ◽  
Kazuma Ikeda ◽  
Nobuhara Fujii ◽  
Kinuyo Kasumoto ◽  
Mitune Tanimoto ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Cell ◽  
Cord Blood ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Jurkat Cells ◽  
Human Cord Blood ◽  
Tumoricidal Activity ◽  
Ifn Γ

Abstract Besides their role as antigen presenting cells, human peripheral blood mononuclear cell and CD34+ cell-derived dendritic cells (DCs), now have been demonstrated to exert cytotoxicity against some tumor cells, and their tumoricidal activity can be enhanced by some stimili. However, there have been no reports concerning the tumor-cell killing activity by human cord blood cell-derived dendritic cells (CBDCs). We report here that human cord blood monocyte-derived DCs aquire the ability to kill tumor cells after activation with lipopolysaccharide (LPS) or interferon-γ(IFN-γ), associated with the enhanced TNF-α-related apoptosis-inducing ligand (TRAIL) expression in CBDC cytoplasm. The CD14-positive cells collected from cord blood from healthy volunteers were cultured with interleukin-4 and granulocyte-machrophage colony- stimulating factor for seven days to induce CBDCs, which showed no cytotoxicity. However, after activation with IFN-γ for additional 12 hours, CBDCs exhibited cytotoxicity against HL60 and Jurkat cells, while activation with LPS for 12 hours induced cytotoxicity against Daudi and Jurkat cells as we detected in human peripheral blood monocytes- drived DCs (PBDCs). IFN-γ or LPS stimulation enhanced intracellular but not cellular surface TRAIL, and neither intracellular nor cellular surface Fas Ligand as analyzed by flow cytometry. Our results suggest that activated CBDCs can serve as immunological effectors against tumor cells, through TRAIL- dependent and Fas-independent mechanisms.

Concentration-dependent dual effect of thrombin on impaired growth/apoptosis or mitogenesis in tumor cells

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3133-3138 ◽  
Author(s):  
Jasmine Zain ◽  
Yao-Qi Huang ◽  
XueSheng Feng ◽  
Mary Lynn Nierodzik ◽  
Jian-Jun Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Calf Serum ◽  
Annexin V ◽  
Tumor Cell Growth ◽  
Diisopropyl Fluorophosphate ◽  
General Caspase Inhibitor

Because thrombin-treated tumor cell-induced metastasis increases tumor nodule volume12 greater than nodule number, we studied the effect of thrombin on tumor cell growth in vitro and in vivo (murine B16F10 melanoma, human HCT8 colon carcinoma, DU145 prostate carcinoma). Tumor cell growth was measured after 3 to 7 days in 1% fetal calf serum (FCS) + RPMI 1640. We found that, whereas relatively low concentrations of thrombin, 0.1 to 0.5 U/mL (1-5 nmol/L) enhance tumor cell growth in vitro approximately 2- to 3-fold, higher concentrations, 0.5 to 1 U/mL (5-10 nmol/L) impaired cell growth approximately 2- to 4-fold. Impaired cell growth was associated with cell cycle arrest at G2M and increased pre-GoDNA, as well as apoptosis, measured by tumor cell binding to Annexin V and propidium iodide. Apoptosis was reversed with the general caspase inhibitor, FK-011. The enhancing and inhibiting effects were specific for thrombin (reversed with inactive diisopropyl-fluorophosphate [DFP]-thrombin) and mediated via the protease-activated receptor 1 (PAR-1). PAR-1 activation was demonstrated by (1) use of a cell line, B16F10, devoid of the 3 other thrombin receptors, PAR-3, PAR-4, and GPIb; and (2) greater sensitivity of PAR-1 transfected B16F10 and HCT8 cells to impaired cell growth/apoptosis, 3- and 14-fold, respectively. Thus, thrombin has a bimodal effect on PAR-1 in tumor cells: enhanced growth at low concentration, impaired growth/apoptosis at higher concentration.

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