A5066840940- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Organ Transplantation Techniques and Outcomes
- Cancer Immunotherapy and Biomarkers
- Renal Transplantation Outcomes and Treatments
- Immunotherapy and Immune Responses
- Inflammatory mediators and NSAID effects
- HIV/AIDS drug development and treatment
- Immune cells in cancer
- CAR-T cell therapy research
- Liver Disease and Transplantation
- Phosphodiesterase function and regulation
- Pneumocystis jirovecii pneumonia detection and treatment
- Reproductive System and Pregnancy
- Transplantation: Methods and Outcomes
- Adenosine and Purinergic Signaling
- Immunodeficiency and Autoimmune Disorders
- Synthesis of Organic Compounds
- Synthesis and biological activity
- Celiac Disease Research and Management
- Pancreatic function and diabetes
- Biochemical and Molecular Research
- Chronic Lymphocytic Leukemia Research
- Hepatocellular Carcinoma Treatment and Prognosis
Oslo University Hospital
2013-2023
University of Oslo
2011-2022
Nord University
2008
Biotechnology Research Center
2007
Technology Centre Prague
2004-2006
University of California, San Francisco
2002-2005
Gladstone Institutes
2002-2005
San Francisco General Hospital
2004
Karolinska University Hospital
2004
Karolinska Institutet
2004
ABSTRACT Regulatory T (T R ) cells maintain tolerance to self-antigens and control immune responses alloantigens after organ transplantation. Here, we show that CD4 + CD25 human suppress virus-specific T-cell responses. Depletion of from peripheral blood mononuclear enhances cytomegalovirus immunodeficiency virus antigens. We propose chronic viral infections lead induction suppressive inhibit the antiviral response.
Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, gut have been considered short lived. this study, we studied PC dynamics human small intestine by cell-turnover analysis organ transplants and retrospective cell birth dating measuring carbon-14 genomic DNA. We identified three distinct subsets: a CD19+ subset was dynamically exchanged, whereas of two CD19- subsets, CD45+ exhibited little CD45- no replacement had...
Macrophages (Mfs) are instrumental in maintaining immune homeostasis the intestine, yet studies on origin and heterogeneity of human intestinal Mfs scarce. Here, we identified four distinct Mf subpopulations small intestine (SI). Assessment their turnover duodenal transplants revealed that all subsets were completely replaced over time; Mf1 Mf2, phenotypically similar to peripheral blood monocytes (PBMos), largely within 3 wk, whereas two with features mature Mfs, Mf3 Mf4, exhibited...
Abstract CD4+CD25+ regulatory T (TR) cells suppress effector by partly unknown mechanisms. In this study, we describe a population of human suppressive adaptive TR (TRadapt) induced in vitro that express cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. TRadapt produce PGE2 cell responses manner is reversed COX inhibitors receptor-specific antagonists. resting CD4+CD25− cells, treatment with FOXP3 expression. Thus, autocrine paracrine effects produced COX-2-positive may be...
Resident memory CD8 T (Trm) cells have been shown to provide effective protective responses in the small intestine (SI) mice. A better understanding of generation and persistence SI Trm humans may implications for intestinal immune-mediated diseases vaccine development. Analyzing normal transplanted human SI, we demonstrated that majority were bona fide survived >1 yr graft. Intraepithelial lamina propria showed a high clonal overlap repertoire dominated by expanded clones, conserved...
Abstract In chronic lymphocytic leukemia (CLL), signaling through several prosurvival B cell surface receptors activates the PI3K pathway. Idelalisib is a highly selective (PI3Kδ) isoform-specific inhibitor effective in relapsed/refractory CLL and follicular lymphoma. However, severe autoimmune adverse effects association with use of idelalisib treatment CLL, particularly as first-line therapy, gave indications that may preferentially target suppressive function regulatory T cells (Tregs)....
Abstract cAMP negatively regulates T cell immune responses by activation of type I protein kinase A (PKA), which in turn phosphorylates and activates C-terminal Src (Csk) lipid rafts. Using yeast two-hybrid screening, far-Western blot, immunoprecipitation immunofluorescense analyses, small interfering RNA-mediated knockdown, we identified Ezrin as the A-kinase anchoring that targets PKA to Furthermore, brings proximity its downstream substrate Csk rafts forming a multiprotein complex...
Continuous antigen stimulation of CD4(+)CD25(-) T cells leads to generation adaptive CD4(+)CD25(+)FOXP3(+) regulatory (T(R)) cells. Here, we show that highly suppressive CD8(+)CD25(+)FOXP3(+) can be generated in the same manner by continuous presence CD14(+) monocytes. During course stimulation, acquisition immunosuppressive properties develops parallel with up-regulation and expression cytotoxic molecules. The CD8(+) T(R) inhibit CD4(+) cell proliferation cytokine production, but do not...
Cyclic AMP-dependent protein kinase A (PKA) type I has been established as an acute inhibitor of T cell activation. For this reason, we investigated the possible role PKA in HIV-induced dysfunction. cells from HIV-infected patients have increased levels cAMP and are more sensitive to inhibition by analog than normal cells. I-selective antagonist increases impaired proliferation or subnormal (up 2.8-fold). Follow-up after initiation highly active antiretroviral treatment revealed that a...
cAMP mediates its intracellular effects through activation of protein kinase A (PKA), nucleotide-gated ion channels, or exchange directly activated by (Epac). Although elevation in lymphocytes leads to suppression immune functions a PKA-dependent mechanism, the effector mechanisms for regulation monocytes and macrophages are not fully understood. In this study, we demonstrate presence Epac1 human peripheral blood Rap1 response cAMP. However, using an Epac-specific analog...
Monocytes initiate innate immune responses and interact with T cells to induce antigen-specific by antigen presentation secretion of humoral factors. We have previously shown that adaptive regulatory inhibit T-cell effector functions in a cyclooxygenase (COX)-2–prostaglandin E2 (PGE2)-dependent manner PGE2 converts resting CD4+CD25− into FOXP3+ suppressive phenotype. Here, we demonstrate stimulation monocytes LPS leads suppression COX-2–PGE2-dependent mechanism is reversible COX-2 inhibitors...
ABSTRACT Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the cell capability. cAMP may be induced prostaglandin E 2 following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type (COX-2) in monocytes due to LPS levels patients infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks HIV-infected without antiretroviral treatment prospective,...
Pancreatic ductal adenocarcinoma (PDAC) is highly infiltrated by CD4+T cells that express RORγt and IL-17 (TH17). Compelling evidence from the tumor microenvironment suggest regulatory T (Treg) contribute to TH17 mediated inflammation. Concurrently, PDAC patients have elevated levels of pro-inflammatory cytokines may lead associated functional plasticity in Treg. In this study, we investigated phenotype properties Treg with PDAC. We report frequency FOXP3+Treg, which exclusively occurred...
Abstract cAMP inhibits biochemical events leading to T cell activation by triggering of an inhibitory protein kinase A (PKA)-C-terminal Src pathway assembled in lipid rafts. In this study, we demonstrate that PKA type I Sp-8-bromo-cAMPS (a agonist) has profound effects on Ag-specific immune responses peripheral effector cells. Activation both cytokine production and proliferative CD4+ CD8+ cells a concentration-dependent manner. The observed appeared occur endogenously were not dependent...
Abstract The adaptive immune response of human CD8 T cells to invading pathogens involves the differentiation naive into memory and effector cells. However, lineage relationship between distinct subsets cell subpopulations are subjects considerable debate. CD7 identifies three populations cells: high (CD7high), low (CD7low), negative (CD7neg) that translate with functional properties. CD7high subset contains CD7low CD7neg contain can functionally be divided cytokine-secreting lytic These...
The molecular mechanisms underlying the T cell dysfunction often present in common variable immunodeficiency (CVI) are not established. cAMP-dependent protein kinase A type I (PKAI) is an important inhibitor of proliferation after Ag stimulation. We therefore investigated possibility that activation PKAI may be involved development CVI. An exogenously added PKAI-selective antagonist (Rp-8-Br-cAMPS) induced a significant increase anti-CD3-stimulated PBMC 20 CVI patients compared with no...