Search results for " T cell"
showing 10 items of 1161 documents
Cytotoxicity of fagaramide derivative and canthin-6-one from Zanthoxylum (Rutaceae) species against multidrug resistant leukemia cells
2019
In our continuous search for cytotoxic compounds from the genus Zanthoxylum, chromatographic separation of the MeOH/CH2Cl2 (1:1) extract of Z. chalybeum yielded one new alkamide; 4-(isoprenyloxy)-3-methoxy-3,4-deoxymethylenedioxyfagaramide (1) and a known one; fagaramide (2). Similarly, from the MeOH/CH2Cl2 (1:1) extract of the stem bark of Z. parachanthum four known compounds; canthin-6-one (3), dihydrochelerythrine (4), lupeol (5) and sesamin (6) were isolated. Characterization of the structures of these compounds was achieved using spectroscopic techniques (NMR and MS). Using resazurin reduction assay 1, 3 and 6 displayed moderate cytotoxicity with IC50 values below 50 μM against the dru…
Antigen dose-dependent suppression of murine IgE responses is mediated by CD4−CD8− double-negative T cells
2010
Background The IgE response against protein antigens is profoundly influenced by the dose used for sensitization. Objective The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation. Methods Wild-type mice as well as T helper (Th)1-deficient IL-12p40(-/-) and IFN-gamma(-/-) mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets …
Cytotoxic alkaloids from the root of Zanthoxylum paracanthum (mildbr) Kokwaro
2021
Chemical investigation of the root of Zanthoxylum paracanthum afforded 1 new alkamide derivative, (2E,4E)-6-oxo-N-isobutyldeca-2,4-dienamide (1) together with 10 known congeners including one pheno...
Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments
2021
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells …
GTPases of the Rho Subfamily Are Required for Brucella abortus Internalization in Nonprofessional Phagocytes
2001
Members of the genus Brucella are intracellular -Proteobacteria responsible for brucellosis, a chronic disease of humans and animals. Little is known about Brucella virulence mechanisms, but the abilities of these bacteria to invade and to survive within cells are decisive factors for causing disease. Transmission electron and fluorescence microscopy of infected nonprofessional phagocytic HeLa cells revealed minor membrane changes accompanied by discrete recruitment of F-actin at the site of Brucella abortus entry. Cell uptake of B. abortus was negatively affected to various degrees by actin, actin-myosin, and microtubule chemical inhibitors. Modulators of MAPKs and protein-tyrosine kinases…
In Vitro Stimulation and Expansion of Human Tumour-Reactive CD8+ Cytotoxic T Lymphocytes by Anti-CD3/CD28/CD137 Magnetic Beads
2011
Adoptive immunotherapy with tumour-reactive CD8(+) cytotoxic T lymphocytes (CTLs) requires efficient in vitro approaches allowing the expansion of CTLs to large numbers prior infusion. Here, we investigated the antigen-independent activation and the expansion of human T cells in peripheral blood mononuclear cells (PBMCs) and in tumour-reactive CTLs using Dynabeads coated with monoclonal antibodies to CD3 and to the costimulatory molecules CD28 and CD137 (4-1BB). T cells in PBMCs showed an increased expansion rate of 15- to 17-fold during a 2-week culture period using antibody-conjugated beads with interleukin-2 (IL-2) added versus IL-2 alone. No significant difference between CD3/CD28 beads…
Nucleoprotein-specific nonneutralizing antibodies speed up LCMV elimination independently of complement and FcγR
2013
CD8(+) T cells have an essential role in controlling lymphocytic choriomeningitis virus (LCMV) infection in mice. Here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (Abs), in this infection induced by low virus inoculation doses. Mice with impaired humoral immunity readily terminated infection with the slowly replicating LCMV strain Armstrong but showed delayed virus elimination after inoculation with the faster replicating LCMV strain WE and failed to clear the rapidly replicating LCMV strain Docile, which is in contrast to the results obtained with wild-type mice. Thus, the requirement for adaptive humoral immunity to control the infection was dep…
Animal models: Murine cytomegalovirus
2002
Publisher Summary This chapter focuses on murine cytomegalovirus (CMV) animal models. Multiple-organ cytomegalovirus disease, interstitial pneumonia in particular, is a major concern in the therapy of hematopoietic malignancies by hematoablative treatment and bone marrow transplantation (BMT). Human CMV (hCMV) is the prototype member of the subfamily, Betaherpesvirinae, of the virus family, Herpesviridae . Its genome is a linear, double-stranded DNA with a coding capacity of ca. 165 open reading frames. During an aeon of co-evolution, CMVs have adapted themselves to their respective hosts; therefore, CMV biology is most reliably studied in a natural virus-host combination. Even though hCMV …
Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…
2015
BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding
Transcutaneous Immunization with a Solid Nanoscopic Imiquimod Suspension Enhances Tumor Rejection
2015
Abstract Introduction: Transcutaneous immunization (TCI) is a novel vaccination strategy to induce strong therapeutic cytotoxic T-lymphocyte (CTL) responses by directly targeting skin-resident professional antigen-presenting cells (APC). This vaccination approach is very promising to overcome current limitations of standard vaccination approaches that are mostly effective in prophylaxis, but not in the treatment of diseases. In this context, we have developed a TCI method based on a synthetic TLR7 agonist imiquimod that partial tumor protection in experimental rodent models. In our present work, we describe a novel optimized formulation of imiquimod in a solid suspension of crystalline imiq…