| dc.contributor.advisor | Brück, Wolfgang Prof. Dr. | |
| dc.contributor.author | Schlosser, Corinna | |
| dc.date.accessioned | 2013-08-28T08:21:14Z | |
| dc.date.available | 2014-01-01T23:50:04Z | |
| dc.date.issued | 2013-08-28 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0001-BB3A-1 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-4014 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Live imaging of autoimmune responses in distinct milieus of the central nervous system | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Brück, Wolfgang Prof. Dr. | |
| dc.date.examination | 2013-06-14 | |
| dc.description.abstracteng | Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system (CNS). Even though it is considered to be a classical demyelinating disease, an increasing body of evidence also demonstrates the early presence of inflammatory lesions in the grey matter. In experimental autoimmune encephalomyelitis (EAE), the animal paradigm of MS, preferential involvement of grey matter is rarely reported, hindering the study of this important aspect of the disease.
In this thesis, green fluorescent protein (GFP)-transduced effector T cells reactive either against a myelin antigen, i.e. the myelin basic protein (TMBP-GFP) or against a neuronal antigen, i.e. the β-synuclein (Tβ-Syn-GFP) were used to induce EAE by passive transfer in recipient Lewis rats. The aim was to elucidate the homing behaviour of encephalitogenic effector T cells into the distinct milieus of the CNS. Both of these T cell lines had a similar phenotype in vitro and similar pathogenic potential in vivo. However, they displayed a completely different infiltration pattern in the CNS tissue: whereas the TMBP-GFP cells were distributed mainly in the white matter, the Tβ-Syn-GFP cells were mostly located in the grey matter of the brain and spinal cord (SC), mimicking the cortical pathology of MS. This divergent infiltration pattern was not due to tissue-intrinsic properties such as apoptosis rate or chemokine expression in the different CNS compartments. Neither did cell-specific properties such as chemokine/integrin expression profile, cytokine level or T cell homing during the preclinical phase play any role. By using two–photon laser scanning microscopy it was possible to visualize in real time the entry and the distribution of TMBP-GFP cells and Tβ-Syn-GFP cells in the meningeal compartments of brain and SC, thus providing indirect evidence that the antigen availability in the target tissue determines the level of activation and therefore the pattern of tissue invasion. Finally, direct activation of TMBP cells in the white matter and of Tβ-Syn cells in the grey matter of the CNS parenchyma was demonstrated in situ by using a genetically encoded NFAT (nuclear factor of T cell activation) biosensor further confirming that the antigen-dependent activation of encephalitogenic T cells is the key factor that determines the homing of these cells into the target tissue. | de |
| dc.contributor.coReferee | Marquardt, Till Dr. | |
| dc.contributor.thirdReferee | Wouters, Fred Prof. Dr. | |
| dc.subject.eng | Experimental Autoimmune Encephalomyelitis | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BB3A-1-6 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.description.embargoed | 2014-01-01 | |
| dc.identifier.ppn | 766542874 | |