Search results for "T cell"
showing 10 items of 2228 documents
Nrf2 expression driven by Foxp3 specific deletion of Keap1 results in loss of immune tolerance in mice
2020
European journal of immunology 50(4), 515-524 (2020). doi:10.1002/eji.201948285
Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex
2019
Polysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (polyST), ST8SIA2 and ST8SIA4, are involved in the synthesis and attachment of polySia. Both polyST are relevant for developmental migration of cortical interneurons and their establishment in the prefrontal cortex (PFC). In contrast, only ST8SIA4 appears to be important for the structural plasticity of a subpopulation of cortical interneurons in the adult. Interestingly, ST8SIA2 and NCAM are candida…
Impact of Cholesterol Metabolism in Immune Cell Function and Atherosclerosis
2020
Cholesterol, the most important sterol in mammals, helps maintain plasma membrane fluidity and is a precursor of bile acids, oxysterols, and steroid hormones. Cholesterol in the body is obtained from the diet or can be de novo synthetized. Cholesterol homeostasis is mainly regulated by the liver, where cholesterol is packed in lipoproteins for transport through a tightly regulated process. Changes in circulating lipoprotein cholesterol levels lead to atherosclerosis development, which is initiated by an accumulation of modified lipoproteins in the subendothelial space; this induces significant changes in immune cell differentiation and function. Beyond lesions, cholesterol levels also play …
Regulatory T Cells Prevent Neutrophilic Infiltration of Skin during Contact Hypersensitivity Reactions by Strengthening the Endothelial Barrier
2020
The healing phase of contact hypersensitivity reactions is critically dependent on regulatory T cells (Tregs), but even the early inflammatory phase, that is, 6-24 hours after induction of a contact hypersensitivity reaction, is susceptible to Treg-mediated suppression. To investigate the underlying mechanisms, we injected Tregs before the challenge and analyzed the skin-infiltrating cells as early as 6 hours later. Early on, we found mainly neutrophils in the challenged skin, but only a few T cells. This influx of neutrophils was blocked by the injection of Tregs, indicating that they were able to prevent the first wave of leukocytes, which are responsible for starting an immune reaction. …
Multi-centre validation of a flow cytometry method to identify optimal responders to interferon-beta in multiple sclerosis.
2018
Background and objectives: Percentages of blood CD19 + CD5 + B cells and CD8 + perforin + T lymphocytes can predict response to Interferon (IFN)-beta treatment in relapsing-remitting multiple sclerosis (RRMS) patients. We aimed to standardize their detection in a multicenter study, prior to their implementation in clinical practice. Methods: Fourteen hospitals participated in the study. A reference centre was established for comparison studies. Peripheral blood cells of 105 untreated RRMS patients were studied. Every sample was analyzed in duplicate in the participating centre and in the reference one by flow cytometry. When needed, participating centres corrected fluorescence compensations…
Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART
2018
Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to s…
Preliminary biomarker and pharmacodynamic data from a phase I study of single-agent bispecific antibody T-cell engager GBR 1302 in subjects with HER2…
2018
69 Background: HER2 is overexpressed in many solid tumors and is a validated therapeutic target. GBR 1302 is a HER2xCD3 bispecific antibody engineered (using Glenmark’s BEAT® platform) to direct T-cells to HER2-expressing tumor cells. GBR1302-101 (NCT02829372) is an ongoing, multicenter, open-label, first-in-human study of GBR 1302 in subjects with HER2-positive cancers to evaluate the safety, tolerability, and preliminary efficacy of GBR 1302, and to elucidate the mechanism(s) by which it redirects T-cells to tumor and enhances cytolytic activity of cytotoxic T-cells. Methods: Adults with progressive HER2-positive solid tumors with no available standard or curative treatment receive intra…
A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments.
2017
We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected with NFAT-luciferase was used to study if changes in PD-L1 expression in cancer cell lines were functionally relevant. Five KRAS mutant cell lines with high PD-L1 expression (H441, H2291, H23, H2030 and A549) were exposed to GI50 inhibitor concentrations of a MEK inhibitor (trametinib) and an AKT inhibitor (AZD5363) for 3 weeks. Only 3/5 (H23, H2030 and A549) and 2/5 cell lines (H441 and H23) showed functionally significant increases in PD-L1 expression when exposed to…
Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospectiv…
2017
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: H…
Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
2019
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. In addition, late relapses are emerging suggesting the development of acquired resistances that compromise the anticancer efficacy of ICI. How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating…