Other
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LanguagesEnglish, German, French
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Scientific MembershipsAmerican Assocation of Immunologists; Germany Society of Neurology
Publications (91) View all
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Article: Statins: a revised appraisal for potential additional future treatment indications.
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ABSTRACT: Beside statins' well established positive influence on atherosclerotic vascular disease caused by hypercholesterolemia through selective competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, additional effects on the immune system have been described for them. These observations have raised great hopes for additional future treatment indications, including rheumatoid arthritis and multiple sclerosis. Ten years of searching for such novel treatment indications have not led to breakthroughs and future efforts must be seen with skepticism.Arthritis research & therapy 06/2012; 14(3):121. · 4.27 Impact Factor -
Article: Autoantigen conformation influences both B- and T-cell responses and encephalitogenicity.
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ABSTRACT: It has become increasingly clear that only antibodies recognizing conformation-dependent epitopes of myelin oligodendrocyte glycoprotein (MOG) have a demyelinating potential in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Nevertheless, for the induction of EAE, most studies to date have used MOG peptides or bacterially expressed MOG, neither of which contain the tertiary structure of the native antigen. Non-refolded recombinant human MOG does not induce EAE in DA rats. Therefore, we refolded this protein in order to assess the influence of MOG conformation on its pathogenicity in DA rats. DA rats immunized with refolded human MOG developed severe acute EAE. As expected, rats immunized with the refolded protein had a higher amount of conformational MOG antibodies present in serum. But in addition, a striking effect of MOG refolding on the generation of T-cell responses was found. Indeed, T-cell responses against the encephalitogenic MOG 91-108 epitope were greatly enhanced after refolding. Therefore, we conclude that refolding of MOG increases its pathogenicity both by generating conformation-dependent MOG antibodies and by enhancing its processing or/and presentation on MHC molecules. These data are important in regard to investigations of the pathogenic potential of many (auto)antigens.Journal of Biological Chemistry 04/2012; 287(21):17206-13. · 4.77 Impact Factor -
Chapter: Experimental Autoimmune Encephalomyelitis
02/2012; , ISBN: 978-953-51-0038-6 -
Article: Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity.
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ABSTRACT: Cladribine (2-chloro-2'-deoxyadenosine) is a purine nucleoside analogue (PNA) which causes targeted and sustained reduction of peripheral lymphocyte counts. Cladribine tablets produced significant treatment benefit for patients with relapsing-remitting multiple sclerosis in the phase 3 CLARITY study. In addition to the well-characterised cell-specific phosphorylation of PNAs responsible for lymphocyte reduction, the mode of action of cladribine may encompass distinct activities contributing to its overall effects on the immune system. Here we demonstrate that clinically relevant concentrations of cladribine also inhibit cytokine secretion by human peripheral blood T cells in vitro through mechanisms independent of the induction of lymphocyte death.Journal of neuroimmunology 12/2011; 240-241:52-7. · 2.84 Impact Factor -
Article: Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.
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ABSTRACT: Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10⁶ MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine, 5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1 × 10⁶ cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their levels in the intact hemisphere. IN administration provides a highly promising noninvasive alternative to the traumatic surgical procedure of transplantation and allows targeted delivery of cells to the brain with the option of chronic application.Rejuvenation Research 02/2011; 14(1):3-16. · 3.83 Impact Factor
