Publications by authors named "Jeroen van Bergen"

CD4 T helper antigens are essential components of cancer vaccines, but the relevance of the source of these MHC class II-restricted antigens remains underexplored. To compare the effectiveness of tumor-specific versus tumor-unrelated helper antigens, we designed three DNA vaccines for the murine MC-38 colon carcinoma, encoding CD8 T cell neoantigens alone (noHELP) or in combination with either "universal" helper antigens (uniHELP) or helper neoantigens (neoHELP). Both types of helped vaccines increased the frequency of vaccine-induced CD8 T cells, and particularly uniHELP increased the fraction of KLRG1 and PD-1 effector cells.

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SARS-CoV-2 is the third zoonotic coronavirus to cause a major outbreak in humans in recent years, and many more SARS-like coronaviruses with pandemic potential are circulating in several animal species. Vaccines inducing T cell immunity against broadly conserved viral antigens may protect against hospitalization and death caused by outbreaks of such viruses. We report the design and preclinical testing of 2 T cell-based pan-sarbecovirus vaccines, based on conserved regions within viral proteins of sarbecovirus isolates of human and other carrier animals, like bats and pangolins.

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Pyroptosis is a recently discovered form of inflammatory programmed necrosis characterized by caspase-1-mediated and gasdermin D-dependent cell death leading to the release of pro-inflammatory cytokines such as Interleukin-1 beta (IL-1β). Here, we evaluated whether pyroptosis could be exploited in DNA vaccination by incorporating a constitutively active variant of caspase-1 to the antigen-expressing DNA. In vitro, transfection with constitutively active caspase-1 DNA induced pro-IL-1β maturation and IL-1β release as well as gasdermin D-dependent cell death.

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Human cytomegalovirus (HCMV) is an ubiquitous herpesvirus that can cause serious morbidity and mortality in immunocompromised or immune-immature individuals. A vaccine that induces immunity to CMV in these target populations is therefore highly needed. Previous attempts to generate efficacious CMV vaccines primarily focused on the induction of humoral immunity by eliciting neutralizing antibodies.

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Celiac disease is an auto-immune disease in which an immune response to dietary gluten leads to inflammation and subsequent atrophy of small intestinal villi, causing severe bowel discomfort and malabsorption of nutrients. The major instigating factor for the immune response in celiac disease is the activation of gluten-specific CD4+ T cells expressing T cell receptors that recognize gluten peptides presented in the context of HLA-DQ2 and DQ8. Here we provide an in-depth characterization of 28 gluten-specific T cell clones.

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The combination of immune-stimulating strategies has the potency to improve immunotherapy of cancer. Vaccination against neoepitopes derived from patient tumor material can generate tumor-specific T cell immunity, which could reinforce the efficacy of checkpoint inhibitor therapies such as anti-PD-1 treatment. DNA vaccination is a versatile platform that allows the inclusion of multiple neoantigen-coding sequences in a single formulation and therefore represents an ideal platform for neoantigen vaccination.

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Article Synopsis
  • Innate lymphoid cells (ILCs) play a crucial role in maintaining tissue health and barrier function in mucosal areas, but their specific differentiation pathways remain largely unexplored.
  • Researchers used mass cytometry to analyze ILCs in the human fetal intestine, uncovering 34 distinct clusters and revealing complex relationships between ILCs and natural killer (NK) cells.
  • An intermediate cell population was identified (LinCD7CD127CD45ROCD56) that can transition into either ILC3 or NK cells, suggesting new insights into ILC differentiation pathways.
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Article Synopsis
  • - Refractory celiac disease type II (RCDII) is a serious form of celiac disease characterized by abnormal lymphocytes in the intestine, which can lead to lymphoma in about half of the patients.
  • - The survival of these abnormal lymphocytes is driven by IL-15 from epithelial cells, and recent findings show that gluten-specific CD4 T cells can also promote their proliferation through cytokines like TNF, IL-2, and IL-21.
  • - Researchers found that targeting specific signaling pathways (JAK/STAT and PI3K/Akt/mTOR) can block the proliferation induced by these cytokines, indicating that CD4 T-cell responses play a significant role in the development of RCDII and
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In HLA-DQ8-associated celiac disease, TRAV26-2-TRBV9 and TRAV8-3-TRBV6 T cells recognize the immunodominant DQ8-glia-α1 epitope, whereupon a non-germline-encoded arginine residue played a key role in binding HLA-DQ8-glia-α1. Whether distinct T cell receptor (TCR) recognition modes exist for gliadin epitopes remains unclear. TCR repertoire analysis revealed populations of HLA-DQ8-glia-α1 and HLA-DQ8.

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Article Synopsis
  • Human NK cells are primarily studied through blood samples, focusing on conventional CD56(bright) and CD56(dim) types, but a new subset has been identified in lymphoid organs.
  • This new NK cell subset, marked by CD69 and CXCR6, makes up 30-60% of NK cells in bone marrow, spleen, and lymph nodes, but is not found in blood.
  • The CD69(+)CXCR6(+) NK cells have unique characteristics, such as intermediate CD56 expression and they require activation to unleash their cytotoxic abilities, distinguishing them from conventional NK cells.
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Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease.

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Objective: Coeliac disease (CD), a gluten-induced enteropathy, alters the composition and function of duodenal intraepithelial T cells. The intestine also harbours four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56(-)CD127(-), CD56(-)CD127(+), CD56(+)CD127(-) and CD56(+)CD127(+). Here we aimed to gain insight into the potential function of these innate IELs in health and disease.

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Article Synopsis
  • In HLA-DQ8-associated celiac disease (CD), T cells respond to a specific peptide from gliadin (DQ8-glia-α1), but details about T cell receptor (TCR) gene usage in affected intestinal tissue are not well understood.
  • Researchers identified two unique populations of CD4(+) T cells in patients, which were not present on a gluten-free diet but expanded rapidly when exposed to the gliadin peptide, particularly distinguishing them by the expression of TRBV9.
  • Both T cell populations showed a similar response to the peptide and utilized specific structural features in their TCRs that are crucial for their interaction with the peptide, highlighting the prevalence of these gluten-specific memory T cells in the intestinal tissue
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Refractory coeliac disease type II (RCDII) is characterized by a continuous gluten-independent duodenal immune activation with an extremely high risk of malignant transformation. It is therefore considered as an indolent lymphoma. RCDII is characterized by the presence of villous atrophy (Marsh III A-C) in combination with an aberrant intra- epithelial lymphocyte (IEL) population consisting of >20% sCD3-CD7+iCD3+ IELs.

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In patients with celiac disease, gluten consumption causes inflammation of the duodenum, and, to a lesser extent, the proximal jejunum. Immune-dominant gluten peptides are modified by the enzyme TG2, leading to their high-affinity binding to HLA-DQ2 or HLA-DQ8 molecules, present in people with a predisposition to celiac disease. Gluten peptide-loaded HLA-DQ2 or HLA-DQ8 molecules are recognized by highly conserved receptors on CD4(+) T cells in the lamina propria.

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Objective: Increased numbers of IL-17-producing CD4(+) T cells have been observed in AS. However, it is not known whether these CD4(+) T cells are already present in early disease or if this is a late disease phenomenon only. Therefore we aimed to investigate whether IL-17-producing CD4(+) T cells are involved in early active axial SpA, including patients without imaging abnormalities, by determining the frequency and phenotype of IL-17-producing CD4(+) T cells in these patients.

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Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.

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Celiac disease (CD) patients who fail to respond to a gluten-free diet suffer from refractory celiac disease (RCD). A marked expansion of intraepithelial lymphocytes (IEL) lacking surface TCR/CD3 expression characterizes the RCD subtype II. In up to 50% of RCDII patients these so-called aberrant IEL (a-IEL) develop into lymphoma and can disseminate into other tissues.

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Aim: To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) to mitigate the immunogenic effects of gluten in celiac patients.

Methods: Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet (GFD) resulting in normalised antibodies and mucosal healing classified as Marsh 0 or I were included. In a randomised double-blind placebo-controlled pilot study, patients consumed toast (approximately 7 g/d gluten) with AN-PEP for 2 wk (safety phase).

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NK cells use NK cell receptors to be able to recognize and eliminate infected, transformed, and allogeneic cells. Human NK cells are prevented from killing autologous healthy cells by virtue of inhibitory NKRs, primarily killer cell Ig-like receptors (KIR) that bind "self" HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand.

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Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T cell-mediated disorder that is induced by dietary gluten. Although it is established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition event that triggers disease pathology. We show that biased TCR usage (TRBV9(∗)01) underpins the recognition of HLA-DQ8-α-I-gliadin.

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Objective: Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease (CD) characterised by aberrant intraepithelial lymphocytes (IELs) of unknown origin that display an atypical CD3(-)CD7(+)icCD3(+) phenotype. In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells.

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Objectives: Aberrant intra-epithelial lymphocytes (IELs) are the hallmark of refractory coeliac disease type II RCDII and considered a premalignant cell population from which aggressive enteropathy-associated T cell lymphoma (EATL) can evolve. The aim of this study was to gain further insight in the origin and characteristics of aberrant IELs by analysing T-cell receptor (TCR) rearrangements, and by immunophenotypic analysis of aberrant IELs.

Design: Duodenal biopsies from 18 RCDII patients and three RCDII cell lines were analysed for the presence of TCR delta, gamma, and beta rearrangements.

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