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Doctoral thesis
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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

ContributorsHumbert, Marion
Defense date2019-01-31
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.

eng
Keywords
  • T cell response
  • Antigen presentation
  • MHC class II
  • Plasmacytoid dendritic cell
  • Lymphatic endothelial cell
  • Lymph node stromal cell
  • Anti-tumor immunity
  • Immunotherapy
  • Cancer
  • CpG: TLR9
  • Autoimmunity
  • Experimental autoimmune encephalomyelitis
  • Multiple sclerosis
Citation (ISO format)
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. 2019. doi: 10.13097/archive-ouverte/unige:115554
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Creation03/13/2019 1:11:00 PM
First validation03/13/2019 1:11:00 PM
Update time03/15/2023 4:04:26 PM
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