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Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells

Kel, J.M. (author), Slütter, B. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo...

article 2008

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Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE

Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)

Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...

article 2008

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Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis

Kel, J. (author), Oldenampsen, J. (author), Luca, M. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP139-151)...

article 2007

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Induction of EAE by T cells specific for alpha B-crystallin depends on prior viral infection in the CNS

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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Protective and therapeutic role for αB-crystallin in autoimmune demyelination

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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αB-Crystallin-reactive T cells from knockout mice are not encephalitogenic

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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Mannosylated PLP139-151 induces peptide-specific tolerance to experimental autoimmune encephalomyelitis

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

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FcR interactions do not play a major role in inhibition of experimental autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies

Nagelkerken, L. (author), Haspels, I. (author), van Rijs, W. (author), Blauw, B. (author), Ferrant, J.L. (author), Hess, D.M. (author), Garber, E.A. (author), Taylor, F.R. (author), Burkly, L.C. (author), Gaubius Instituut TNO (author)

It has been demonstrated that anti-CD154 mAb treatment effectively inhibits the development of experimental autoimmune encephalomyelitis (EAE). However, although it appears to prevent the induction of Th1 cells and reactivation of encephalitogenic T cells within the CNS, little information is available regarding the involvement of alternative...

article 2004

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Non-invasive measurement of brain damage in a primate model of multiple sclerosis

'T Hart, B.A. (author), Vogels, J. (author), Bauer, J. (author), Brok, H.P.M. (author), Blezer, E. (author), TNO Voeding (author)

Early recognition of whether a product has potential as a new therapy for treating multiple sclerosis (MS) relies upon the quality of the animal models used in the preclinical trials. The promising effects of new treatments in rodent models of experimental autoimmune encephalomyelitis (EAE) have rarely been reproduced in patients suffering from...

article 2004

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1H-NMR spectroscopy combined with pattern recognition analysis reveals characteristic chemical patterns in urines of MS patients and non-human primates with MS-like disease

't Hart, B.A. (author), Vogels, J.T.W.E. (author), Spijksma, G. (author), Brok, H.P.M. (author), Polman, C. (author), van der Greef, J. (author), Primatencentrum TNO (author)

Proton nuclear magnetic resonance (1H-NMR) spectroscopy in combination with pattern recognition techniques were used to investigate the composition of organic compounds in urines from patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and healthy controls (H). Using a valid animal model of MS, namely the...

article 2003

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T- and B-cell nonresponsiveness to self-αB-crystallin in SJL mice prevents the induction of experimental allergic encephalomyelitis

van Stipdonk, M.J.B. (author), Willems, A.A. (author), Verbeek, R. (author), Boog, C.J.P. (author), van Noort, J.M. (author), TNO Preventie en Gezondheid (author)

The myelin-associated stress protein αB-crystallin triggers strong proliferative responses and IFN-γ production by human T cells and it is considered a candidate autoantigen in multiple sclerosis. In this study we examined the capacity of αB-crystallin or peptides derived thereof to induce experimental autoimmune encephalomyelitis (EAE) in SJL...

article 2000

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Tolerance controls encephalitogenicity of αB-crystallin in the Lewis rat

van Stipdonk, M.J.B. (author), Willems, A.A. (author), Plomp, A.C. (author), van Noort, J.M. (author), Boog, C.J.P. (author), TNO Preventie en Gezondheid (author)

The myelin-associated protein, αB-crystallin, is considered a candidate autoantigen in multiple sclerosis (MS). In the present study, we examined the potential of αB-crystallin to induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Attempts to induce EAE with either bovine, rat or murine αB-crystallin or αB-crystallin peptides...

article 2000

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IFN-beta modulates specific T cell responses in vitro but does not affect Experimental Autoimmune Encephalomyelitis in the SJL mouse

Luca, M.E. (author), Visser, L. (author), Lucas, C.J. (author), Nagelkerken, L. (author), TNO Preventie en Gezondheid (author)

In this study, mouse recombinant IFN-β was shown to favor PLP139-151-specific Th2 responses in vitro, by inhibiting IFN-γ production and stimulating IL-4 and IL-10 production. IFN-β (5000 U/day) failed to prevent the development or severity of EAE induced with PLP139-151. Whereas efficacy of IL-10 was found in the B. pertussis assisted but not...

article 1999

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Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis

TNO Preventie en Gezondheid (author), Howard, L.M. (author), Miga, A.J. (author), Vanderlugt, C.L. (author), Dal Canto, M.C. (author), Laman, J.D. (author), Noelle, R.J. (author), Miller, S.D. (author)

Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis and is characterized by infiltration of the central nervous system (CNS) by Th1 cells and macrophages. Disease relapses are mediated by T cells specific for endogenous myelin epitopes...

article 1999

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CD40 in clinical inflammation: From multiple sclerosis to atherosclerosis

Laman, J.D. (author), de Boer, M. (author), 't Hart, B.A. (author), TNO Preventie en Gezondheid (author)

The interactions of CD40 and CD40L have been known for some time to critically regulate B-cell responses with respect to proliferation, isotype switching, antibody production, and memory formation. More recent findings demonstrated that CD40 can be expressed on several other antigen-presenting cell (APC) types such as macrophages, dendritic...

article 1998

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Antigen-specific therapies in multiple sclerosis

van Noort, J.M. (author), TNO Preventie en Gezondheid (author)

Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is stripped off axons by infiltrated macrophages...

article 1998

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Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide

Laman, J.D. (author), Maassen, C.B.M. (author), Schellekens, M.M. (author), Visser, L. (author), Kap, M. (author), de Jong, E. (author), van Puijenbroek, M. (author), van Stipdonk, M.J.B. (author), van Meurs, M. (author), Schwärzler, C. (author), Günthert, U. (author), TNO Preventie en Gezondheid (author)

Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154,...

article 1998

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Balancing the Th1/Th2 concept in multiple sclerosis

Laman, J.D. (author), Thompson, E.J. (author), Kappos, L. (author), TNO Preventie en Gezondheid (author)

article 1998

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Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman, J.D. (author), van Meurs, M. (author), Schellekens, M.M. (author), de Boer, M. (author), Melchers, B. (author), Massacesi, L. (author), Lassmann, H. (author), Claassen, E. (author), 't Hart, B.A. (author), TNO Preventie en Gezondheid (author)

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected...

article 1998

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Orally administered Lactobacillus strains differentially affect the direction and efficacy of the immune response

Maassen, C.B.M. (author), van Holten, J.C.A.M. (author), Balk, F. (author), Heijne den Bak-Glashouwer, M.J. (author), Leer, R. (author), Laman, J.D. (author), Boersma, W.J.A. (author), Claassen, E. (author), TNO Preventie en Gezondheid (author)

In mice, strain dependent cytokine production profiles are induced after oral administration of Lactobacillus. Such a cytokine profile seems to determine the direction and efficacy of the humoral response. In SJL mice lactobacilli are able to enhance or inhibit the development of disease after induction of experimental autoimmune...

article 1998