A5016948656- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Immune Response and Inflammation
- Cellular transport and secretion
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Extracellular vesicles in disease
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- HIV Research and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Toxoplasma gondii Research Studies
- Cytomegalovirus and herpesvirus research
- interferon and immune responses
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
University Hospital Schleswig-Holstein
2014-2024
University of Lübeck
2014-2024
Kiel University
2012-2023
Institute of Immunology
1990-2017
University Medical Centre Mannheim
2014
Heidelberg University
1990-2014
Clinical Research Center Kiel
2003-2009
Centre d’Immunologie de Marseille-Luminy
2005
Centre National de la Recherche Scientifique
2005
Georg Speyer Haus
2005
Signaling via the CD3/TCR complex induces programmed cell death (apoptosis) in immature thymocytes and transformed T lymphocytes (hybridomas or leukemic cells). Accumulating evidence indicates, however, that apoptosis can be triggered also mature peripheral cells. Here we show a significant fraction of cells given IL-2-dependent TCR-alpha beta + clone polyclonal short term line is killed when cultured for 20 h presence PHA, anti-CD3 (OKT3), anti-TCR (BMA031) mAb. Apoptosis by these stimuli...
Insulin resistance (IR) and central obesity are common features of the polycystic ovary syndrome (PCOS). Vitamin D is thought to play a role in pathogenesis type 2 diabetes by affecting insulin metabolism. The aim our study was investigate effect 25-hydroxyvitamin (25-OH-VD) on metabolic parameters IR PCOS. In 120 untreated PCOS patients (median age 28 years) levels 25-OH-VD (radioimmunoassay method provided DiaSorin), calcium anorganic phosphate were measured. addition, endocrine variables...
Fas (APO-1/CD95) is the prototypic death receptor, and molecular mechanisms of Fas-induced apoptosis are comparably well understood. Here, we show that activates NFkappaB via a pathway involving RIP, FADD, caspase-8. Remarkably, enzymatic activity latter was dispensable for signaling pointing to scaffolding-related function caspase-8 in nonapoptotic signaling. activated by overexpressed FLIPL FLIPS cell type-specific manner. However, context both isoforms blocked FasL-induced activation....
The Src-related tyrosine kinase p59fyn(T) plays an important role in the generation of intracellular signals from T-cell antigen receptor TCR zeta/CD3 complex. A key question concerns nature and binding sites downstream components that interact with this kinase. contains Src-homology 2 3 domains (SH2 SH3) a capacity to bind proteins. One potential target is phosphatidylinositol 3-kinase (PI 3-kinase). In study, we demonstrate anti-CD3 anti-Fyn immunoprecipitates possess PI activity as...
We have previously reported that peripheral blood gamma/delta + T cells proliferate in high frequency (1 2-20) response to heat-killed Mycobacterium tuberculosis (M.tb.). In the present study, cell receptor phenotype of mycobacteria-responsive human was analyzed primary cultures with a set monoclonal antibodies (mAbs) directed against V gamma 9, delta 1, and 2. When unseparated were stimulated M.tb., all proliferating expressed 9 (and 2) after culture. Selective depletion 9-bearing before...
The interaction of the MHC class I-related chain molecules A and B (MICA MICB) with corresponding natural killer group 2, member D (NKG2D) receptor triggers cytotoxic effector activity cells certain T-cell subsets provides a costimulatory signal for cytokine production. Thus, presence MICA/B on transformed contributes to tumor immunosurveillance. Consequently, proteolytic cleavage is regarded as an important immune escape mechanism various cancer cells. To investigate molecular machinery...
mAb directed against the TCR/CD3 complex activate resting T cells. However, signaling induces death by apoptosis in immature (CD4+CD8+) murine thymocytes and certain transformed leukemic cell lines. Here we show that anti-TCR anti-CD3 induce growth arrest of cloned TCR-gamma delta + cells presence IL-2. In absence exogenous IL-2, however, very same anti-TCR/CD3 stimulated gamma (+)-clones to proliferation IL-2 production. induced degradation DNA into oligosomal bands approximately 200 bp...
Abstract γδ T lymphocytes play an important role in the immune defense against infection, based on unique reactivity of human Vδ2Vγ9 cells toward bacterial phosphoantigens. Chemokines and their corresponding receptors orchestrate numerous cellular reactions, including leukocyte migration, activation, degranulation. In this study we investigated expression various for inflammatory homeostatic chemokines peripheral blood compared patterns with those αβ cells. Although several analyzed...
Src homology 3 (SH3) domains have been recently shown to bind proline-rich sequences contained in 3BP1, 3BP2, and SOS. In a recent study we demonstrated that phosphatidylinositol 3-kinase (PI 3-kinase) associates with the Fyn SH3 domain. Here show p85, regulatory subunit of PI 3-kinase, binds directly Abl, Lck, Fyn, p85 itself. An examination amino acid sequence revealed two its N-terminal region similar those present To test whether these mediate association peptides composition...
CD4 serves as a receptor for major histocompatibility complex class II antigens and the human immunodeficiency virus type 1 (HIV-1) viral coat protein gp120. It is coupled to protein-tyrosine kinase p56lck, an interaction necessary optimal response of certain T cells antigen. In addition domain, p56lck possesses Src homology 2 3 (SH2 SH3) domains well unique N-terminal region. The mechanism by which generates intracellular signals unclear, although it has potential interact with various...
Nck is a ubiquitously expressed adapter protein that almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins are functionally redundant in many aspects differ only few amino acids mostly located the linker regions between interaction modules. proteins connect receptor non-receptor tyrosine kinases to machinery actin reorganisation. Thereby, regulates activation-dependent processes during cell polarisation migration plays crucial role signal transduction variety...
The TNF receptor superfamily member CD95 (Fas, APO-1, TNFRSF6) is known as the prototypic death in and outside immune system. In fact, many mechanisms involved apoptotic signaling cascades were solved by addressing consequences pathways initiated ligation activated T cells or other "CD95-sensitive" cell populations. As an example, binding of inducible ligand (CD95L) to on lymphocytes results death. This activation-induced was implicated control homeostasis response termination. Over past...
The interaction of the MHC class I-related chain molecules A and B (MICA MICB) UL-16 binding protein (ULBP) family members expressed on tumor cells with corresponding NKG2D receptor triggers cytotoxic effector functions in NK γδ T cells. However, as a mechanism immune escape, ligands (NKG2DLs) can be released from cell surface. In this study, we investigated NKG2DL system different human glioblastoma (GBM) lines, most lethal brain adults. Flow cytometric analysis ELISA revealed that despite...
In apoptosis, proteolysis by caspases is the primary mechanism for both initiation and execution of programmed cell death (PCD). contrast, impact on regulation caspase-independent forms PCD (programmed necrosis, necroptosis) only marginally understood. Likewise, identity involved proteases has remained largely obscure. Here, we have investigated in TNF-induced necroptosis.The serine protease inhibitor TPKC protected from necroptosis multiple murine human cells systems whereas inhibitors...
TGF-β is a pleiotropic cytokine with multiple roles in immunity. Apart from its suppressive activity, driving the differentiation of induced regulatory T cells (iTreg) but also polarization interleukin-9 (IL-9) producing helper 9 (Th9) cells. Human Vδ2 expressing γδ exert potent cytotoxicity towards variety solid tumor and leukemia/lymphoma target thus are focus current strategies to develop cell-based immunotherapies. Here we report that unexpectedly augments cytotoxic effector activity...