scholarly journals Immune Reactions Against Elongation Factor 2 Kinase: Specific Pathogenesis of Gastric Ulcer fromHelicobacter pyloriInfection

2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
Kiyoshi Ayada ◽  
Kenji Yokota ◽  
Yoshiro Kawahara ◽  
Yumiko Yamamoto ◽  
Kazuyuki Hirai ◽  
...  
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Specific Antigen ◽  
Elongation Factor ◽  
Causative Factor ◽  
Gastric Ulcers ◽  
Target Cells ◽  
Effector Cells ◽  
Elongation Factor 2 ◽  
H Pylori

Helicobacter pylori(H. pylori) infection is a definite causative factor for gastric ulcers (GUs). In the present study we detected a specific antigen of gastric epithelial cells (HGC-27) using cell ELISA, which was recognized by the sera of GU patients (n=20) but not in patients with chronic gastritis (CG;n=20) or in healthy volunteers (HC;n=10). This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients' lymphocytes stimulated byH. pylorispecifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes) from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1) and cytotoxic T lymphocyte (CTL) as opposed to those from CG patients. The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU.

Chronic gastroduodenal ulcers in patients with diabetes mellitus

2003 ◽  
Vol 49 (1) ◽  
pp. 5-10
Author(s):  
Yu. L. Fedorchenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Clinical Course ◽  
Gastrin Level ◽  
Gastric Ulcers ◽  
Peptic Ulcers ◽  
Duodenal Ulcers ◽  
Patients With Diabetes ◽  
H Pylori

The clinical picture, course, and treatment of gastroduodenal ul­cers (GDU) in diabetics were studied. A total of 395 diabetics were examined; GDU were detected in 36. The incidence of gas­tric and duodenal ulcers was similar in patients with insulin-de­pendent diabetes mellitus, while in patients with non-insulin-de- pendent diabetes gastric ulcers predominated. The clinical pic­ture of the disease, gastric acid production, Helicobacter pylori infection, and blood gastrin levels were studied in all patients with ulcers. The efficiency of GDU treatment with quamatel, raniti­dine, and antacids was evaluated. The clinical course of GDU in diabetics was asymptomatic. The highest incidence of H. pylori, infection was observed in patients with type 1 diabetes with con­comitant peptic ulcers. Serum gastrin levels were more frequently increased in patients with type 1 diabetes and duodenal ulcers and normal in patients with type 2 diabetes. Quamatel therapy was highly effective in diabetics with GDU. Ulcers healed in 85% patients and blood gastrin level significantly decreased after 3- week therapy. GDU in diabetics are characterized by specific lo­cation, clinical course, laboratory and instrumental features, which allows a differentiated approach to therapy of these pa­tients.

scholarly journals A Novel System for the Quantification of the ADCC Activity of Therapeutic Antibodies

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Christophe Lallemand ◽  
Feifei Liang ◽  
Flore Staub ◽  
Maud Simansour ◽  
Benoit Vallette ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Matrix Effects ◽  
Specific Antigen ◽  
Firefly Luciferase ◽  
Cell Number ◽  
Target Cells ◽  
The Novel ◽  
Adcc Activity ◽  
Effector Cells ◽  
High Level

Novel ADCC effector cells expressing the V-variant or F-variant of FcγRIIIa (CD16a) and firefly luciferase under the control of a chimeric promoter incorporating recognition sequences for the principal transcription factors involved in FcγRIIIa signal transduction, together with novel target cells overexpressing a constant high level of the specific antigen recognized by rituximab, trastuzumab, cetuximab, infliximab, adalimumab, or etanercept, confer improved sensitivity, specificity, and dynamic range in an ADCC assay relative to effector cells expressing a NFAT-regulated reporter gene and wild-type target cells. The effector cells also contain a normalization gene rendering ADCC assays independent of cell number or serum matrix effects. The novel effector and target cells in a frozen thaw-and-use format exhibit low vial-to-vial and lot-to-lot variation in their performance characteristics reflected by CVs of 10% or less. Homologous control target cells in which the specific target gene has been invalidated by genome editing providing an ideal control and a means of correcting for nonspecific effects were observed with certain samples of human serum. The novel effector cells and target cells expressing noncleavable membrane-bound TNFα have been used to quantify ADCC activity in serum from patients with Crohn’s disease treated with infliximab and to relate ADCC activity to drug levels.

scholarly journals The target cell nucleus is not required for cell-mediated granzyme- or Fas-based cytotoxicity.

1995 ◽  
Vol 181 (5) ◽  
pp. 1905-1909 ◽  
Author(s):  
H Nakajima ◽  
P Golstein ◽  
P A Henkart
Keyword(s):  
Cell Death ◽  
Target Cell ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Cell Nuclei ◽  
Effector Cells ◽  
Cell Death Pathways ◽  
Mast Cell Tumors ◽  
Nuclear Damage

The requirement for target cell nuclei in the two apoptotic death pathways used by cytotoxic lymphocytes was tested using model effector systems in which the granzyme and Fas pathways of target damage are isolated. Mast cell tumors expressing granzymes A and B in addition to cytolysin/perforin lysed tumor target cells about 10-fold more efficiently than comparable effector cells without granzymes. Enucleated cytoplast targets derived from these cells were also lysed with a similar 10-fold effect of granzymes. In contrast to cytoplasts, effector granzyme expression did not influence lysis of red cell targets. The Fas pathway was assessed using the selected cytotoxic T lymphocyte hybridoma subline d11S, which lysed target cells expressing Fas but not those lacking Fas. Similarly, cytoplasts derived from Fas+ but not Fas- cells were also readily lysed by these effector cells. Thus, neither the nucleus itself nor the characteristic apoptotic nuclear damage associated with the two major cell death pathways used by cytotoxic lymphocytes are required for cell death per se.

scholarly journals Antibody from Patients with Acute Human Immunodeficiency Virus (HIV) Infection Inhibits Primary Strains of HIV Type 1 in the Presence of Natural-Killer Effector Cells

2001 ◽  
Vol 75 (15) ◽  
pp. 6953-6961 ◽  
Author(s):  
Donald N. Forthal ◽  
Gary Landucci ◽  
Eric S. Daar
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antibody Response ◽  
Natural Killer ◽  
Effector Cell ◽  
Target Cells ◽  
Effector Cells ◽  
Viremia Level ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The partial control of viremia during acute human immunodeficiency virus type 1 (HIV-1) infection is accompanied by an HIV-1-specific cytotoxic T-lymphocyte (CTL) response and an absent or infrequent neutralizing antibody response. The control of HIV-1 viremia has thus been attributed primarily, if not exclusively, to CTL activity. In this study, the role of antibody in controlling viremia was investigated by measuring the ability of plasma or immunoglobulin G from acutely infected patients to inhibit primary strains of HIV-1 in the presence of natural-killer (NK) effector cells. Antibody that inhibits virus when combined with effector cells was present in the majority of patients within days or weeks after onset of symptoms of acute infection. Furthermore, the magnitude of this effector cell-mediated antiviral antibody response was inversely associated with plasma viremia level, and both autologous and heterologous HIV-1 strains were inhibited. Finally, antibody from acutely infected patients likely reduced HIV-1 yield in vitro both by mediating effector cell lysis of target cells expressing HIV-1 glycoproteins and by augmenting the release of β-chemokines from NK cells. HIV-1-specific antibody may be an important contributor to the early control of HIV viremia.

scholarly journals Chronic gastroduodenal ulcers in patients with diabetes mellitus

2003 ◽  
Vol 49 (1) ◽  
pp. 5-10
Author(s):  
Yu. L. Fedorchenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Clinical Course ◽  
Gastrin Level ◽  
Gastric Ulcers ◽  
Peptic Ulcers ◽  
Duodenal Ulcers ◽  
Patients With Diabetes ◽  
H Pylori

The clinical picture, course, and treatment of gastroduodenal ul­cers (GDU) in diabetics were studied. A total of 395 diabetics were examined; GDU were detected in 36. The incidence of gas­tric and duodenal ulcers was similar in patients with insulin-de­pendent diabetes mellitus, while in patients with non-insulin-de- pendent diabetes gastric ulcers predominated. The clinical pic­ture of the disease, gastric acid production, Helicobacter pylori infection, and blood gastrin levels were studied in all patients with ulcers. The efficiency of GDU treatment with quamatel, raniti­dine, and antacids was evaluated. The clinical course of GDU in diabetics was asymptomatic. The highest incidence of H. pylori, infection was observed in patients with type 1 diabetes with con­comitant peptic ulcers. Serum gastrin levels were more frequently increased in patients with type 1 diabetes and duodenal ulcers and normal in patients with type 2 diabetes. Quamatel therapy was highly effective in diabetics with GDU. Ulcers healed in 85% patients and blood gastrin level significantly decreased after 3- week therapy. GDU in diabetics are characterized by specific lo­cation, clinical course, laboratory and instrumental features, which allows a differentiated approach to therapy of these pa­tients.

scholarly journals CD4+ Cytotoxic T-Lymphocyte Activity against Macrophages Pulsed with Bovine Herpesvirus 1 Polypeptides

1998 ◽  
Vol 72 (9) ◽  
pp. 7040-7047 ◽  
Author(s):  
Chong Wang ◽  
Gary A. Splitter
Keyword(s):  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Bovine Herpesvirus ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Bovine Herpesvirus 1 ◽  
Effector Cells ◽  
Herpesvirus 1

ABSTRACT Bovine herpesvirus 1 (BHV-1) induces immune suppression, but the mechanisms for suppression are not well identified. We examined the induction and activity of BHV-1-specific cytolytic CD4+ T lymphocytes (CTL) by stimulating peripheral blood mononuclear cells (PBMC) of cattle immunized with attenuated live BHV-1. Cytolytic effector cells were primarily CD4+ T lymphocytes and lysed autologous, but not allogeneic, macrophages infected with BHV-1 or pulsed with BHV-1 polypeptides. Apoptosis of BHV-1-expressing target cells was observed in CD4+ CTL assays by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) analysis. To determine if apoptosis was mediated by a perforin- or Fas-mediated pathway, EGTA, a known selective inhibitor of the perforin pathway, was used. EGTA did not inhibit CD4+-T-cell-mediated cytotoxic activity, but it did limit the NK cell cytotoxicity of virus infected cells. These findings support the concept that CD4+ CTL lyse macrophages pulsed with BHV-1 polypeptides through a Fas-mediated lytic pathway by inducing apoptosis in the target cells. The prominent cytotoxicity mediated by CD4+ CTL suggests a mechanism of selective removal of viral antigen-associated antigen-presenting cells.

scholarly journals Regulation of in vitro cytotoxic T lymphocyte generation. I. Evidence that killer cell precursors differentiate to effector cells in two steps.

1982 ◽  
Vol 155 (3) ◽  
pp. 783-796 ◽  
Author(s):  
A Schwartz ◽  
S L Sutton ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Killer Cell ◽  
Suppressor Cells ◽  
Target Cells ◽  
Suppressor T Cells ◽  
Effector Cells ◽  
Step Process

The differentiation of cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells is a two-step process. In the first step, naïve CTL-P (CTL-PN) become activated (CTL-PA) but do not yet have the capacity to kill target cells. CTL-PA can be distinguished from CTL-PN because the former are far less sensitive than the latter to the effects of in vitro-generated suppressor cells. Thus, the addition of suppressor T cells (Ts) to a fresh MLC can totally inhibit the production of CTL from CTL-PN, whereas the same Ts only minimally affect the generation of CTL from CTL-PA. It is not known whether these Ts act directly on CTL-PN or on a helper cell needed for activation to CTL-PA. The production of CTL-PA can take place in allogeneic mixed leukocyte cultures (MLC) treated with the drug pyrilamine, or when heat-inactivated stimulator cells are used. Each of these treatments inhibits the differentiation of CTL-PA to CTL. However, if pyrilamine is removed, a nonspecific MLC-derived signal can induce these CTL-PA to become CTL, even in the presence of significant numbers of Ts. This two step process of differentiation of CTL-P to CTL may be analogous to the way naïve B cells become antibody-producing cells.

scholarly journals Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120

2000 ◽  
Vol 74 (1) ◽  
pp. 326-333 ◽  
Author(s):  
Karl Salzwedel ◽  
Erica D. Smith ◽  
Barna Dey ◽  
Edward A. Berger
Keyword(s):  
Human Immunodeficiency Virus ◽  
Membrane Fusion ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Target Cells ◽  
Effector Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Soluble Cd4

ABSTRACT We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Envs from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems.

scholarly journals Role of extracellular adenosine triphosphate in the cytotoxic T- lymphocyte-mediated lysis of antigen presenting cells

Blood ◽  
1995 ◽  
Vol 85 (11) ◽  
pp. 3173-3182 ◽  
Author(s):  
DK Blanchard ◽  
S Wei ◽  
C Duan ◽  
F Pericle ◽  
JI Diaz ◽  
...  
Keyword(s):  
Immune Response ◽  
Adenosine Triphosphate ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Ifn Gamma ◽  
Effector Cells ◽  
Antigen Presenting

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma-activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.

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