Teun Guichelaar

National Institute for Public Health and the Environment (RIVM) | RIVM · Centre for Infectious Disease Control (CIb)

Aging leads to alterations in the immune system that result in ineffective responsiveness against pathogens. Features of this process, collectively known as immunosenescence, accumulate in CD8+ T cells with age and have been ascribed to differentiation of these cells during the course of life. Here we aimed to identify novel markers in CD8+ T cells...

Severe respiratory viral infectious diseases such as influenza and COVID-19 especially affect the older population. This is partly ascribed to diminished CD8⁺ T-cell responses a result of aging. The phenotypical diversity of the CD8⁺ T-cell population has made it difficult to identify the impact of aging on CD8⁺ T-cell subsets associated with dimin...

Decline of immune function during aging has in part been ascribed to the accumulation of regulatory T cells (Tregs) and decreased T-cell responses with age. Aside from changes to T cells that occur over a lifetime, the impact of intracellular aging processes such as compromised DNA repair on T cells remains incompletely defined. Here we aimed to de...

Disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans. However, causality and underlying mechanisms have not yet been established. In this study, we exposed hyperlipidemic APOE*3‐Leiden.CETP mice to either regular light‐dark cycles, weekly 6 h phase advances or delays, or weekly alternating‐...

The impact of ageing on the immune system results in defects in T cell responsiveness. The search for ageing hallmarks has been challenging due to the complex nature of immune responses in which the kinetics of T cell responsiveness have largely been neglected. We aimed to unravel hallmarks of ageing in the kinetics of the murine T cell response. T...

Abstract Aging poses an increased risk of severe infection by respiratory syncytial virus (RSV). The many different biological pathways comprising the response to infection in lungs that are influenced by aging are complex and remain to be defined more thoroughly. Towards finding new directions in research on aging, we aimed to define biological pa...

Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed to define aging-related changes of the immune sys...

Gelijkwaardigheid van mannen en vrouwen is vaak nog ver te zoeken, óók in de muziekwereld anno 2017. Des te wranger is het daarom dat muziekjournalisten klakkeloos de vervreemdende aanduiding ‘all-female’ blijven gebruiken. Maar wat zit er precies achter die aanduiding? En is het benadrukken van ‘all-female’ misschien zelfs in het vóórdeel van de s...

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory illness in infants. At this young age, infants typically depend on maternally transferred antibodies (matAbs) and their innate immune system for protection against infections. RSV-specific matAbs are thought to protect from severe illness, yet severe RSV disease occurs mai...

Respiratory syncytial virus (RSV) is the leading cause for respiratory illness that requires hospitalization in infancy. High levels of maternal antibodies can protect against RSV infection. However, RSV-infected infants can suffer from severe disease symptoms even in the presence of high levels of RSV-specific antibodies. This study analyzes sever...

Supporting information depicting all individual data. (XLS)

Cellular damage accumulation is a central feature of aging, resulting in functional decline and increased vulnerability to pathology and disease. This accumulation occurs over time, but is not exclusively time-dependent. Recent studies showed that, concerning biomedical issues, age may rather be defined as biological age, expressed as the cumulativ...

Unlabelled: Elderly humans are prone to severe infection with human respiratory syncytial virus (HRSV). The aging of today's human population warrants the development of protective vaccination strategies aimed specifically at the elderly. This may require special approaches due to deteriorating immune function. To design and test vaccination strat...

Development of live-attenuated human respiratory syncytial virus (HRSV) vaccines has proven difficult. Several vaccine candidates were found to be over-attenuated and displayed limited immunogenicity. We recently identified three synthetic cationic lipopeptides that enhanced paramyxovirus infections in vitro. The infection enhancement proved to be...

Regulatory T cells (Tregs) can prevent graft-vs.-host disease as induced by the infusion of donor lymphocytes to cancer patients, but often they also suppress therapeutic antitumor immunity. We discuss an exception to this phenomenon, exemplifying how the milieu provided by the bone marrow may neutralize Tregs to allow local immune responses agains...

Purpose: Regulatory T cells (Tregs) are potent tools to prevent graft-versus-host disease (GVHD) induced after allogeneic stem cell transplantation or donor lymphocyte infusions. Toward clinical application of Tregs for GVHD treatment, we investigated the impact of Tregs on the therapeutic graft-versus-tumor (GVT) effect against human multiple mye...

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Background Regulatory T cells (Treg) are important to maintain immune homeostasis. Presence of Treg correlates with a favourable disease course in juvenile idiopathic arthritis (JIA) patients. A distinction within the Treg population can be made between naturally occurring Treg (nTreg), which are derived from the thymus, and peripherally induced Tr...

1017 While application of regulatory T-cells (Tregs) has become a promising tool to prevent Graft-versus-Host Disease (GvHD), Tregs pose the risk of suppressing the curative Graft-versus-Tumor (GvT) effect induced by therapeutically transfused donor lymphocytes. Towards clinical application of Tregs, we explored the in vivo impact of human Tregs on...

The essential role of CD4(+) T cells as helpers of anticancer immunity is indisputable. Little is known, however, about their capacity to serve as effector cells in cancer treatment. Therefore, we explored the efficacy of immunotherapy with sole CD4(+) cytotoxic human T cells directed at a hematopoietic-restricted minor histocompatibility antigen (...

Immune responses to certain heat-shock proteins (HSP) develop in virtually all inflammatory diseases; however, the significance of such responses is only now becoming clear. In models of experimental arthritis, HSPs can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory diseases, including rh...

Regulatory T cells (Tregs) are a specific subset of lymphocytes that are critical for the maintenance of self-tolerance. Expression levels of the transcription factor Foxp3 have been causally associated with Treg differentiation and function. Recent studies show that Foxp3 can also be transiently expressed in effector T cells; however, stable Foxp3...

1333 Poster Board I-355 The curative Graft versus Tumor (GvT) effect of allogeneic stem cell transplantation and donor lymphocyte infusions is mainly mediated by donor derived T cells recognizing minor Histocompatibility antigens (mHag) presented by malignant cells. Traditionally, CD8+ cytotoxic T cells (CTLs) are considered as “the” effector cells...

Systemic administration of agents that neutralize or antagonize Th1-mediated pro-inflammatory responses has been demonstrated to ameliorate inflammation in chronic autoimmune disease. However, systemic administration of such immunosuppressive biologicals causes serious side effects and has only limited success. To minimize these side effects, autoa...

The propagation of mucosal tolerance as a therapeutic approach in autoimmune diseases remains a difficult goal to achieve, and therefore further mechanistic studies are necessary to develop potential clinical protocols to induce mucosal regulatory T cells (Tr cells). In this study we addressed whether oral or nasal proteoglycan induced functional T...

Deficient T cell regulation can be mechanistically associated with development of chronic autoimmune diseases. Therefore, combining the regulatory properties of IL-10 and the specificity of autoreactive CD4+ T cells through adoptive cellular gene transfer of IL-10 via autoantigen-specific CD4+ T cells seems an attractive approach to correct such de...

The significance of immune responses to certain heat shock proteins (HSPs) that develop in virtually all inflammatory diseases is only now becoming clear. In experimental models, HSPs prevent or arrest inflammatory damage, and initial clinical trials in chronic inflammatory disease have shown HSP peptides to promote production of anti-inflammatory...

To better understand the role of antigen (arthritogenic epitope)-specific T cells in the development of autoimmune arthritis. A transgenic (Tg) mouse expressing the T cell receptor (TCR) Valpha1.1 and V(beta)4 chains specific for a dominant arthritogenic epitope (designated 5/4E8) of human cartilage proteoglycan (HuPG) aggrecan was generated. This...

The movement protein (MP) of Cowpea mosaic virus (CPMV) forms tubules through plasmodesmata in infected plants thus enabling virus particles to move from cell to cell. Localization studies of mutant MPs fused to GFP in protoplasts and plants identified several functional domains within the MP that are involved in distinct steps during tubule format...

Immersion vaccination is common practice in aquaculture, because of its convenience for mass vaccination with sufficient protection. However, the mechanisms of antigen uptake and presentation, resulting in a protective immune response and the role of the innate immune system therein are largely unknown. The impact of immersion vaccination on fish p...

Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not restrict to the autoimmune response, but increases th...