Regulation of CNS inflammation upon T cell interaction with CNS resident cells

Abstract

Multiple Sclerosis (MS), is a neurologic, autoimmune disease characterized by CNS immune cell infiltration and demyelination. To experimentally study MS, we have utilized the mouse model Experimental Autoimmune Encephalomyelitis (EAE). EAE is induced through immunization with myelin antigens, which elicits an autoreactive Th1 cell response. Encephalitogenic T cells migrate into the CNS where they receive antigen specific restimulation via CNS specific APCs, which causes inflammation and demyelination. Our aim with the present study was to investigate various aspects of T cell regulation in EAE. The potential immunoregulatory role of CD1d restricted T cells was evaluated using CD1d deficient mice (CD1-/-). Our results suggests that CD1d restricted T cells regulate EAE, both through down-regulation of peripheral autoreactive T cell cytokine responses and through up-regulation of TGF-beta1 production within the CNS. Next, we investigated the regulatory pathway mediated by IFN-beta, a common treatment for MS. From the results we concluded that IFN-beta is expressed in the CNS upon inflammation, where it represses glial cell activation and capacity to re-stimulate infiltrating encephalitogenic T cells. Furthermore, we could show that IFN-beta increases the glial cell expression of CD1d. IFN-beta has also been implicated to be important in the induction of oral tolerance, however, by using IFN-beta-/- mice and EAE, we showed that oral tolerance induction is not dependent on IFN-beta. Finally, in a study designed to evaluate possible immunoregualatory functions of neurons, we demonstrated that upon interaction with TGF-beta1 producing neurons, encephalitogenic T cells aquire a regulatory phenotype with the capacity to inhibit EAE development.

• author: Teige, Ingrid
• supervisor: [unknown] [unknown]
• opponent: Wekerle, Hartmut, Max Planck institute of Neurobiology, Germany
• organization: Immunology (research group)
• publishing date: 2004
• type: Thesis
• publication status: published
• subject: Immunology in the medical area
• keywords: Neurology, neuropsychology, neurofysiologi, neuropsykologi, Neurologi, neurophysiology, neuron, glia, CNS, T cell, cytokine, immunoregulation, MS, EAE
• pages: 180 pages
• defense location: N/A
• defense date: 2004-11-12 13:00:00
• ISBN: 91-268-6283-9
• language: English
• LU publication?: yes
• additional info: Article: I. Teige A*, Teige I*, Lavasani S, Bockermann R, Mondoc E, Holmdahl R, Issazadeh-Navikas S. “CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis.”J Immunol. 2004 Jan 1;172(1):186-94.* Equal contribution Article: II. Teige I, Treschow A, Teige A, Mattsson R, Navikas V, Leanderson T, Holmdahl R, Issazadeh-Navikas S. “IFN-b gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis”J Immunol. 2003 May 1;170(9):4776-84. Article: III. Teige I, Liu Y, Issazadeh-Navikas S. “IFN-b inhibits T cell activation capacity of CNS Antigen Presenting Cells”.Manuscript (submitted for publication) Article: IV. Teige I, Liu Y, Issazadeh-Navikas S. “Endogenous IFN-b is not crucial for induction of oral tolerance to MBP in experimental autoimmune encephalomyelitis”.Manuscript Article: V. Liu Y, Teige I, Issazadeh-Navikas S. “Neurons; highly immune competent cells: Neurons generate TGF-b+ CD25+ CTLA-4+ regulatory T cells from encephalitogenic T cells”.Manuscript The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
• id: bfd9d8c4-410a-4707-936e-d71d720dc8b5 (old id 467455)
• date added to LUP: 2016-04-04 12:17:43
• date last changed: 2018-11-21 21:10:08