A5052631009- Immune Cell Function and Interaction
- Virus-based gene therapy research
- CAR-T cell therapy research
- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- Immunodeficiency and Autoimmune Disorders
- Wnt/β-catenin signaling in development and cancer
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Allergic Rhinitis and Sensitization
- Cancer-related gene regulation
- COVID-19 Clinical Research Studies
- Mesenchymal stem cell research
- Respiratory viral infections research
- RNA Interference and Gene Delivery
- Iron Metabolism and Disorders
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Food Allergy and Anaphylaxis Research
- DNA Repair Mechanisms
- Gene expression and cancer classification
- Immunotherapy and Immune Responses
- Pregnancy and preeclampsia studies
- Hemoglobinopathies and Related Disorders
Janssen (Netherlands)
2020-2024
Leiden University Medical Center
2009-2019
Erasmus MC
2001-2012
Erasmus University Rotterdam
1992-2012
Institute of Neuroimmunology of the Slovak Academy of Sciences
2008
Erasmus MC - Sophia Children’s Hospital
1994-1997
Rotterdam University of Applied Sciences
1997
To gain more insight into initiation and regulation of T cell receptor (TCR) gene rearrangement during human development, we analyzed TCR rearrangements by quantitative PCR analysis in nine consecutive developmental stages, including CD34+ lin− cord blood cells as a reference. The same stages were used for expression profiling using DNA microarrays. We show that loci rearrange highly ordered way (TCRD-TCRG-TCRB-TCRA) the initiating Dδ2-Dδ3 occurs at most immature CD34+CD38−CD1a− stage. TCRB...
Safe and effective coronavirus disease–19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve magnitude durability of immunity protective efficacy. We assessed one- two-dose Ad26.COV2.S candidate in adult aged nonhuman primates (NHPs). A regimen induced higher peak binding neutralizing antibody responses compared with a single dose. In one-dose regimens, were stable for at least...
Background The immunological processes in early life and their relation to allergic sensitization leading a Th2 cytokine profile are still not well understood. Objective To analyse the environmental genetic risk factors responses at birth development of atopic disease 12 months age longitudinal study high‐risk children. Methods High‐risk children were followed from till age. Mononuclear cells obtained 6 thereafter analysed for proliferative after polyclonal allergen‐specific stimulation....
Wnt signaling is essential for T cell development in the thymus, but stages which it occurs and molecular mechanisms underlying responsiveness have remained elusive. Here we examined activity both human murine thymocyte populations by determining beta-catenin levels, Tcf-reporter activation expression of Wnt-target genes. We demonstrate that all subsets, including more mature populations, most prominently double negative (DN) subsets. This differential sensitivity to was not caused...
The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates nuclear response to Wnt signals. Tcf1−/− mice have previously been characterized show developmental blocks at CD4−CD8− double negative (DN) CD4+CD8+ positive transition. Due development, normally a very small thymus. Unexpectedly, large proportion of spontaneously develop thymic lymphomas with 50% developing lymphoma/leukemia age 16 wk. These are clonal, highly metastatic, paradoxically high signaling...
Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster non-human primate infection models. Here, investigated the immunogenicity, protective efficacy, potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S moderate challenge model, using currently most prevalent G614 variant. Vaccine...
Abstract The thymus is seeded by very small numbers of progenitor cells that undergo massive proliferation before differentiation and rearrangement TCR genes occurs. Various signals mediate these cells, including Wnt signals. induce the interaction cytoplasmic cofactor β-catenin with nuclear T cell factor (TCF) transcription factors. We identified target Wnt/β-catenin/TCF pathway in most immature (CD4−CD8−CD34+) thymocytes using Affymetrix DNA microarrays combination three different...
Abstract The replacement of bone marrow (BM) as a conventional source stem cell (SC) by umbilical cord blood (UCB) and granulocyte-colony stimulating factor-mobilized peripheral SC (PBSC) has brought about clinical advantages. However, several studies have demonstrated that UCB CD34+ cells PBSC significantly differ from BM qualitatively quantitatively. Here, we quantified the number in purified BM, cells, using vitro vivo assays for human hematopoietic (HSC) activity. A cobblestone...
The Wnt-responsive transcription factor T cell 1 (Tcf1) is well known for its role in thymic development and the formation of memory CD8(+) cells. However, initial phases effector has remained unexplored. We report that high levels Wnt signaling Tcf1 are operational naive cells, whereas were low cells deficient produce IFN-γ more rapidly, coinciding with increased demethylation enhancer higher expression factors Tbet Blimp1. Moreover, virus-specific Tcf1(-/-) show accelerated expansion acute...
Adequate responsiveness of CD8(+) T cell populations is utmost importance for the efficacy many vaccines and immunotherapeutic strategies against intracellular pathogens cancer. In this study, we show in mouse models that relative number IL-2-producing cells within Ag-specific predicts population expansion capacity upon challenge. We further demonstrate IL-2 producers constitute best responding subset. Notably, elevated production by results concomitant improved immunity. The amount produced...
During inflammation, membrane expression of adhesion molecules and tumor necrosis factor (TNF)‐receptors (TNF‐R) are increased, soluble forms these released. This study analyzed plasma levels ofsICAM‐1 sE‐selectin as well TNF‐γ, sTNF‐R55, sTNF‐R75 in nonallergic (NAA) allergic asthma patients (AA), atopic dermatitis (AD), healthy children (HC) by ELISA. Plasma sICAM‐1. sE‐selectin. sTNF‐R, but not were detectable, significantly different between the patient groups children. In AA group, a...