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Modulation of peripheral T cell responses by unconventional antigen-presenting cells: role of plasmacytoid dendritic cells in anti-tumor immunity and lymphatic endothelial cells in autoimmunity

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Defense Thèse de doctorat : Univ. Genève, 2019 - Sc. 5308 - 2019/01/31
Abstract The aim of this thesis was to characterize the role of plasmacytoid dendritic cells (pDCs) and lymphatic endothelial cells (LECs) in the modulation of peripheral T cell responses, with a particular focus on MHC class II-restricted antigen presentation. Depending on the immunological context, pDC MHCII-mediated antigen-presenting functions can be either tolerogenic or immunogenic. For instance, pDCs are maintained in a tolerogenic state by the tumor microenvironment. In the first part of this thesis, we asked the question whether tumor-associated pDCs could undergo a tolerogenic-to-immunogenic reprogramming following the intratumoral administration of CpG-B, a TLR9 ligand, along with a model MHC-II-restricted tumor antigenic peptide. LECs from lymph nodes (LN-LECs) were shown to impact peripheral CD8+ T cell responses, as antigen-presenting cells (APCs). Emerging evidence is in favor of a role for LN-LECs in CD4+ T cell tolerance to MHC-II-restricted antigens, although this phenomenon is still a matter of debate. In the second part of this thesis, we sought to determine the contribution of LN-LECs as MHC-II-restricted APCs to autoreactive CD4+ T cell responses in experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis.
Keywords T cell responseAntigen presentationMHC class IIPlasmacytoid dendritic cellLymphatic endothelial cellLymph node stromal cellAnti-tumor immunityImmunotherapyCancerCpG: TLR9AutoimmunityExperimental autoimmune encephalomyelitisMultiple sclerosis
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URN: urn:nbn:ch:unige-1155544
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Thesis (11.7 MB) - public document Free access
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Research group Pathologie et immunologie (906)
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HUMBERT, Marion. Modulation of peripheral T cell responses by unconventional antigen-presenting cells: role of plasmacytoid dendritic cells in anti-tumor immunity and lymphatic endothelial cells in autoimmunity. Université de Genève. Thèse, 2019. doi: 10.13097/archive-ouverte/unige:115554 https://archive-ouverte.unige.ch/unige:115554

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Deposited on : 2019-04-01

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