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Titel: Translational aspects of postischaemic inflammation
Sonstige Titel: Translationale Aspekte der postischämischen Entzündungsreaktion
Sprache: Englisch
Autor*in: Thom, Vivien
GND-Schlagwörter: SchlaganfallGND
ImmunologieGND
EntzündungGND
T-LymphozytGND
Neutrophiler Granulozyt
CytokineGND
Erscheinungsdatum: 2012
Tag der mündlichen Prüfung: 2013-06-06
Zusammenfassung: 
This study was designed to gain further insight into the pathophysiologic events following ischaemic stroke in humans and to find evidence for the transferability of the mice findings to humans. We analysed peripheral blood and CSF leukocytes as well as the sera of patients suffering from acute ischaemic stroke. We furthermore aimed to characterise phenotypical and functional properties of γδ T cells from healthy donors and performed in vitro stimulation of brain endothelial cells with IL-17.
We found that the peripheral blood of stroke patients reflected both the inflammatory immune reaction in the brain and the following systemic immunosuppression. We observed an increase of neutrophils and a decline of T cytotoxic as well as T helper cells, but the number of γδ T cells remained unaltered. Despite the decline in numbers, T cells displayed an activated phenotype, which was most pronounced in the Vδ2 cells. Additionally, we successfully expanded the CSF γδ T cells of some stroke patients, but could not detect significant IL-17 production by these cells. Further efforts to explore the requirements for the induction of IL-17 producing γδ T cells from healthy donors remained unsuccessful. We were not able to induce IL-17 production in Vδ2γ9 cells. Still, we were able to detect markers associated with IL-17 production. Concerning the neutrophils, we found an increase of NET production, which is associated with neutrophil activation. We also showed that stimulation with IL-17 increased the production of neutrophil-chemoattractants by brain endothelial cells. Considering our results and current literature there is abundant evidence for the involvement of IL-17 and neutrophils in the pathophysiology of postischaemic inflammation. The source of the IL-17 in this context, however, is not known yet. We could neither find enough evidence for nor against the pivotal role of γδ T cells, like it has been proposed in the mouse model. It is crucial to first identify the physiological requirements for IL-17 production by γδ T cells in humans, before further exploring their role in the pathophysiology of postischaemic inflammation.
URL: https://ediss.sub.uni-hamburg.de/handle/ediss/5016
URN: urn:nbn:de:gbv:18-62957
Dokumenttyp: Dissertation
Betreuer*in: Tolosa, Eva (PD Dr.)
Enthalten in den Sammlungen:Elektronische Dissertationen und Habilitationen

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