Search results for "Elitis"
showing 10 items of 226 documents
The Eradication of Poliomyelitis in Spain: Projects, Obstacles, Achievements, Realities
2015
he main aim of our paper is to provide a historical approach to the complex process undertaken in Spain to achieve the official WHO certificate of polio eradication in 2002, within the framework of the initiatives launched in the WHO European Region. At the time of the first meeting of the European Regional Commission for the Certification of Poliomyelitis Eradication in 1996, the epidemiological situation and levels of vaccination cover (over 90%) enabled Spain, like other countries, to ensure compliance with the conditions set by the World Health Organization. This showed that the country, at the end of the twentieth century, had achieved high public health standards, which is remarkable …
Apoptosis of oligodendrocytes via Fas and TNF-R1 is a key event in the induction of experimental autoimmune encephalomyelitis.
2005
Abstract In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, immunization with myelin Ags leads to demyelination and paralysis. To investigate which molecules are crucial for the pathogenesis of EAE, we specifically assessed the roles of the death receptors Fas and TNF-R1. Mice lacking Fas expression in oligodendrocytes (ODCs) were generated and crossed to TNF-R1-deficient mice. To achieve specific deletion of a loxP-flanked fas allele in ODCs, we generated a new insertion transgene, expressing the Cre recombinase specifically in ODCs. Fas inactivation alone as well as the complete absence of TNF-R1 protected mice partially from EAE induced by the imm…
Derivatives of Erythropoietin That Are Tissue Protective But Not Erythropoietic
2004
Erythropoietin (EPO) is both hematopoietic and tissue protective, putatively through interaction with different receptors. We generated receptor subtype–selective ligands allowing the separation of EPO's bioactivities at the cellular level and in animals. Carbamylated EPO (CEPO) or certain EPO mutants did not bind to the classical EPO receptor (EPOR) and did not show any hematopoietic activity in human cell signaling assays or upon chronic dosing in different animal species. Nevertheless, CEPO and various nonhematopoietic mutants were cytoprotective in vitro and conferred neuroprotection against stroke, spinal cord compression, diabetic neuropathy, and experimental autoimmune encephalomyeli…
MAPK3 deficiency drives autoimmunity via DC arming.
2010
DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3(-/-) mice have a significantly higher membrane expression of CD86 and MHC-II and--when loaded with the myelin oligodendrocyte glycoprotein--show a superior capacity to prime naive T cells towards an inflammatory phenotype than Mapk3(+/+) DC. Nonetheless and as previously described, Mapk3(-/-) mice were only slightly but not significantly more susceptible to myelin oligodendrocyt…
Modulation of Neurological Deficits and Expression of Glutamate Receptors during Experimental Autoimmune Encephalomyelitis after Treatment with Selec…
2013
The aim of our investigation was to characterize the role of group I mGluRs and NMDA receptors in pathomechanisms of experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. We tested the effects of LY 367385 (S-2-methyl-4-carboxyphenylglycine, a competitive antagonist of mGluR1), MPEP (2-methyl-6-(phenylethynyl)-pyridine, an antagonist of mGluR5), and the uncompetitive NMDA receptor antagonists amantadine and memantine on modulation of neurological deficits observed in rats with EAE. The neurological symptoms of EAE started at 10-11 days post-injection (d.p.i.) and peaked after 12-13 d.p.i. The protein levels of mGluRs and NMDA did not increase in early phases of EAE (4 d.p…
Animal models of Multiple Sclerosis
2015
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which involves a complex interaction between immune system and neural cells. Animal modeling has been critical for addressing MS pathogenesis. The three most characterized animal models of MS are (1) the experimental autoimmune/allergic encephalomyelitis (EAE); (2) the virally-induced chronic demyelinating disease, known as Theiler׳s murine encephalomyelitis virus (TMEV) infection and (3) the toxin-induced demyelination. All these models, in a complementary way, have allowed to reach a good knowledge of the pathogenesis of MS. Specifically, EAE is the model which better reflects the autoimmu…
Mouse models for multiple sclerosis: historical facts and future implications.
2011
AbstractMultiple sclerosis (MS) is an inflammatory and demyelinating condition of the CNS, characterized by perivascular infiltrates composed largely of T lymphocytes and macrophages. Although the precise cause remains unknown, numerous avenues of research support the hypothesis that autoimmune mechanisms play a major role in the development of the disease. Pathologically similar lesions to those seen in MS can be induced in laboratory rodents by immunization with CNS-derived antigens. This form of disease induction, broadly termed experimental autoimmune encephalomyelitis, is frequently the starting point in MS research with respect to studying pathogenesis and creating novel treatments. M…
Primary oligodendrocyte death does not elicit anti-CNS immunity.
2012
Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the initial trigger of this autoreactivity remains elusive. One of the proposed factors for initiating this disease is the primary death of oligodendrocytes. To specifically test such oligodendrocyte death as a trigger for anti-CNS immunity, we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia-macrophage activation followed oligodendrocyte death, and myelin components in draining lymph nodes made CNS antigens available to lymphocytes. However, even conditions favoring autoimmunity-bystander activation, removal of regulatory T cells, presence of myelin-reactive T cells and application of dem…
A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis.
2019
Precision therapy for immune tolerance Autoimmune diseases, such as multiple sclerosis (MS), result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. Current treatments can cause systemic immune suppression and side effects such as increased risk of infections. Krienke et al. designed a messenger RNA vaccine strategy that lacks adjuvant activity and delivers MS autoantigens into lymphoid dendritic cells. This approach expands a distinct type of antigen-specific effector regulatory T cell that suppresses autoreactivity against targeted autoantigens and promotes bystander suppression of autoreactive T cells against other myelin-specific autoantigen…
Autoantibody depletion ameliorates disease in murine experimental autoimmune encephalomyelitis.
2013
Much data support a role for central nervous system antigen-specific antibodies in the pathogenesis of multiple sclerosis (MS). The effects of inducing a decrease in (auto)antibody levels on MS or experimental autoimmune encephalomyelitis (EAE) through specific blockade of FcRn, however, remain unexplored. We recently developed engineered antibodies that lower endogenous IgG levels by competing for binding to FcRn. These Abdegs ("antibodies that enhance IgG degradation") can be used to directly assess the effect of decreased antibody levels in inflammatory diseases. In the current study, we show that Abdeg delivery ameliorates disease in an EAE model that is antibody dependent. Abdegs could…