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van Wijk, F. (author), Nierkens, S. (author), de Jong, W. (author), Wehrens, E.J.M. (author), Boon, L. (author), van Kooten, P. (author), Knippels, L.M.J. (author), Pieters, R. (author), TNO Kwaliteit van Leven (author)Dendritic cells are believed to play an essential role in regulating the balance between immunogenic and tolerogenic responses to mucosal Ags by controlling T cell differentiation and activation via costimulatory and coinhibitory signals. The CD28/CTLA-4-CD80/CD86 signaling pathway appears to be one of the most important regulators of T cell...article 2007
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van Wijk, F. (author), Wehrens, E.J.M. (author), Nierkens, S. (author), Boon, L. (author), Kasran, A. (author), Pieters, R. (author), Knippels, L.M.J. (author), TNO Kwaliteit van Leven (author)Background: Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a critical role in the maintenance of self-tolerance and it has been suggested that these Tregs may also be involved in preventing allergic disease. Objective: The precise role of CD4+CD25+ T cells in the regulation of allergic responses to mucosal antigens remains to be...article 2007
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Bernhagen, J. (author), Krohn, R. (author), Lue, H. (author), Gregory, J.L. (author), Zernecke, A. (author), Koenen, R.R. (author), Dewor, M. (author), Georgiev, I. (author), Schober, A. (author), Leng, L. (author), Kooistra, T. (author), Fingerle-Rowson, G. (author), Ghezzi, P. (author), Kleemann, R. (author), McColl, S.R. (author), Bucala, R. (author), Hickey, M.J. (author), Weber, C. (author), TNO Kwaliteit van Leven (author)The cytokine macrophage migration inhibitory factor (MIF) plays a critical role in inflammatory diseases and atherogenesis. We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF. MIF triggered G αi- and integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin activation and calcium influx...article 2007
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van Wijk, F. (author), Knippels, L. (author), TNO Kwaliteit van Leven (author)Immediately after birth the mucosa of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a large variety of foreign antigens. The immune system of the intestine now has to meet the task of discriminating between pathogens and harmless antigens, such as food proteins...article 2007
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Verbeek, R. (author), van Dongen, H. (author), Wawrousek, E.F. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven TNO Defensie en Veiligheid (author)While myelin-reactive T cells are widely believed to play a pathogenic role in multiple sclerosis (MS), no substantial differences appear to exist in T-cell responses to myelin antigens between MS patients and healthy subjects. As an example, indistinguishable peripheral T-cell responses and serum antibody levels have been found in MS patients...article 2007
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Ousman, S.S. (author), Tomooka, B.H. (author), van Noort, J.M. (author), Wawrousek, E.F. (author), O'Conner, K. (author), Hafler, D.A. (author), Sobel, R.A. (author), Robinson, W.H. (author), Steinman, L. (author), TNO Kwaliteit van Leven (author)αB-crystallin (CRYAB) is the most abundant gene transcript present in early active multiple sclerosis lesions, whereas such transcripts are absent in normal brain tissue. This crystallin has anti-apoptotic and neuroprotective functions. CRYAB is the major target of CD4+ T-cell immunity to the myelin sheath from multiple sclerosis brain. The...article 2007
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Verbeek, R. (author), van der Mark, K. (author), Wawrousek, E.F. (author), Plomp, A.C. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire...article 2007
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TNO Kwaliteit van Leven (author), van der Hoorn, J.W.A. (author), Kleemann, R. (author), Havekes, L.M. (author), Kooistra, T. (author), Princen, H.M.G. (author), Jukema, J.W. (author)AIM: This study was designed to investigate the effect of the angiotensin II receptor blocker olmesartan alone, or in combination with standard treatment with a statin, pravastatin, on atherosclerosis development in APOE*3Leiden transgenic mice. METHODS AND RESULTS: Four groups of 15 mice received an atherogenic diet alone (plasma cholesterol 17...article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Pires, N.M.M. (author), van Mierlo, G.J.D. (author), Kleemann, R. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)BACKGROUND - Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated...article 2007
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van Erk, M.J. (author), Blom, W.A.M. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)Background: Application of transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of specific diets or nutrients and result in biomarker profiles. Objective: The aim was to evaluate the potential of gene expression profiling in blood cells collected in a human intervention study...article 2006
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van Noort, J.M. (author), Verbeek, R. (author), Meilof, J.F. (author), Polman, C.H. (author), Amor, S. (author), TNO Kwaliteit van Leven (author)Human T-cell responses to the stress protein alpha B-crystallin in multiple sclerosis (MS)-affected brain samples are dominant when compared to other myelin antigens. The establishment of the apparent autoimmune repertoire against this antigen has been suggested to involve cross-priming during viral infection. Yet, another possibility would be...article 2006
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Verhaagh, S. (author), de Jong, E. (author), Goudsmit, J. (author), Lecollinet, S. (author), Gillissen, G. (author), de Vries, M. (author), van Leuven, K. (author), Que, I. (author), Ouwehand, K. (author), Mintardjo, R. (author), Weverling, G.J. (author), Radošević, K. (author), Richardson, J. (author), Eloit, M. (author), Lowik, C. (author), Quax, P. (author), Havenga, M. (author), TNO Kwaliteit van Leven (author)Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here, it is reported that CD46 transgenic mice (MYII...article 2006
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Schepers, A. (author), de Vries, M.R. (author), van Leuven, C.J. (author), Grimbergen, J.M. (author), Holers, V.M. (author), Daha, M.R. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)BACKGROUND - Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated...article 2006
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Hu, L. (author), Boesten, L.S.M. (author), May, P. (author), Herz, J. (author), Bovenschen, N. (author), Huisman, M.V. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)OBJECTIVE - In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND RESULTS - We generated...article 2006
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Arts, J.H.E. (author), Mommers, C. (author), de Heer, C. (author), TNO Kwaliteit van Leven (author)A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of...article 2006
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Hartgers, F.C. (author), Smits, H.H. (author), van der Kleij, D. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)Helminth infections have profound effects on the immune system. Here, recent insights in the molecular interactions between schistosomes and the host are described with respect to adaptive but also with respect to innate immune responses. Furthermore, the different mechanisms of immune hyporesponsiveness are depicted with emphasis on regulatory...article 2006
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Wang, C. (author), Chou, Y.K. (author), Rich, C.M. (author), Link, J.M. (author), Afentoulis, M.E. (author), van Noort, J.M. (author), Wawrousek, E.F. (author), Offner, H. (author), van den Bark, A.A. (author), TNO Kwaliteit van Leven (author)Alpha B-crystallin (αB) is a small heat shock protein that is strongly up-regulated in multiple sclerosis (MS) brain tissue, and can induce strong T cell responses. Assessing a potential encephalitogenic function for αB protein in MS and experimental autoimmune encephalomyelitis (EAE) has been challenging due to its ubiquitous expression that...article 2006
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TNO Kwaliteit van Leven (author), Lemckert, A.A.C. (author), Grimbergen, J. (author), Smits, S. (author), Hartkoorn, E. (author), Holterman, L. (author), Berkhout, B. (author), Barouch, D.H. (author), Vogels, R. (author), Quax, P. (author), Goudsmit, J. (author), Havenga, M.J.E. (author)Recombinant adenoviral vectors based on type 5 (rAd5) show great promise as a vaccine carrier. However, neutralizing activity against Ad5 is prevalent and high-titred among human populations, and significantly dampens Ad5-based vaccine modalities. The generation of alternative adenoviral vectors with low seroprevalence thus receives much...article 2006
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Meeuwsen, S. (author), Persoon-Deen, C. (author), Bsibsi, M. (author), Bajramovic, J.J. (author), Ravid, R. (author), de Bolle, L. (author), van Noort, J.M. (author), Gaubius Instituut TNO (author)Human herpesvirus-6A (HHV-6A) is a common pathogen whose role in CNS disorders including multiple sclerosis remains controversial. To understand how HHV-6A could influence inflammatory pathways in the CNS, we infected cultured human adult astrocytes and examined the expression of 268 cytokines, chemokines, growth factors and their receptors by...article 2005
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Luca, M.E. (author), Kel, J.M. (author), van Rijs, W. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), Gaubius Instituut TNO (author)SJL mice immunized with mannosylated (M-) PLP139-151 in complete adjuvant do not develop EAE and little CNS mononuclear cell infiltration; other mannosylated peptides were ineffective in this experimental setting. Despite apparently normal T cell responses, M-PLP139-151-immunized mice show impaired delayed-type-sensitivity to PLP139-151 but a...article 2005