Migratory Cues For Encephalitogenic Effector T Cells Within The CNS During The Different Phases Of EAE

Schläger, Christian

dc.contributor.advisor	Flügel, Alexander Prof. Dr.	de
dc.contributor.author	Schläger, Christian	de
dc.date.accessioned	2013-06-17T09:23:36Z	de
dc.date.available	2014-01-02T23:50:04Z
dc.date.issued	2013-06-17	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-001E-FE91-A	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-3891
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Migratory Cues For Encephalitogenic Effector T Cells Within The CNS During The Different Phases Of EAE	de
dc.type	doctoralThesis	de
dc.contributor.referee	Reichardt, Holger Prof. Dr.	de
dc.date.examination	2013-04-30	de
dc.description.abstracteng	In multiple sclerosis (MS), encephalitogenic T cells are considered to breach distinct cerebral barriers in order to gain access to their target tissue, the CNS. However, it remains poorly understood exactly how auto-reactive T cells overcome these boundaries and which migratory cues guide them on their journey. In the present work, intravital two-photon laser scanning microscopy (TPLSM) was employed to examine in detail the migratory behavior of adoptively transferred GFP+ CD4+ MBP-reactive T cells under the influence of chemokine signaling during different disease phases of experimental autoimmune encephalomyelitis (EAE), an animal model for MS. During preclinical EAE, encephalitogenic effector T cells were crawling along the intraluminal surface of leptomeningeal blood vessels preferentially against the direction of the blood stream. Intravenous administration of pertussis toxin (PTx) or a neutralizing anti-CXCR3mAb revealed that chemokines play an essential role for this intravascular crawling behavior. (1) Intraluminal crawling was almost completely abolished; (2) the remaining fraction of cells profoundly changed their motility characteristics, i.e. they crawled for a shorter time with increased velocity and reversed their orientation to go with instead of against the flow. Once myelin-reactive T cells had transgressed the vascular barriers they continued their migration throughout the meningeal surface. Interference with chemokine signaling at this stage had only a moderate impact on the basal T cell motility. However, chemokines were important for stabilizing the contacts between T cells and resident phagocytes and furthermore prevented the detachment of T cells from the meningeal surface into the cerebrospinal fluid (CSF). In sum, the data indicate that encephalitogenic T cells invade the CNS through a well-coordinated sequence of distinct steps, in which chemokines play a major role. Chemokines regulate effector T cell infiltration by controlling adhesion-dependent migratory steps and intercellular interactions during CNS inflammation.	de
dc.contributor.coReferee	Simons, Mikael Prof. Dr.	de
dc.subject.eng	EAE	de
dc.subject.eng	MS	de
dc.subject.eng	Chemokines	de
dc.subject.eng	T cells	de
dc.subject.eng	TPLSM	de
dc.subject.eng	intravascular crawling	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-001E-FE91-A-6	de
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Immunologie / Allergologie / Umweltmedizin / Medizinische Ökologie - Allgemein- und Gesamtdarstellungen (PPN619875445)	de
dc.description.embargoed	2014-01-02	de
dc.identifier.ppn	749703202	de

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