Philipp, Marie-Sophie: MAIT cell diversity, function and impact on dendritic cells. - Bonn, 2020. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Melbourne.
Online-Ausgabe in bonndoc:
author = {{Marie-Sophie Philipp}},
title = {MAIT cell diversity, function and impact on dendritic cells},
school = {{Rheinische Friedrich-Wilhelms-Universität Bonn} and {University of Melbourne}},
year = 2020,
month = apr,

note = {T cells represent an important component of the immune system. Whilst early studies were largely focused on the role of conventional CD8+ and CD4+ T cells that recognize peptide-antigens in association with MCH molecules, more recently, T cells that recognize other types of antigens have been described. Mucosal associated invariant T (MAIT) cells are such a cell population and belong to the broad family known as ‘unconventional’ T cells, due to their non-peptidic antigen recognition characteristics. MAIT cells are defined by their recognition of microbial vitamin B2 metabolites presented by MHC related protein 1 (MR1). Upon antigen recognition they immediately display effector functions, like secreting cytokines and expression of cytotoxic proteins. Whilst the majority of MAIT cell studies have focused on the role of MAIT cells to bacterial infections, however their function within the immune system and interaction with other immune cells is still unknown. This thesis focuses on the role that MAIT cell activation has on other immune cells like dendritic cells (DCs) and other T cells. Furthermore, the full potential of MR1-recognition by other T cell subsets was also examined, revealing that MR1-reactive T cells may extend beyond what is currently describe as MAIT cells.
The first chapter of this thesis investigates the role of MAIT cell activation on DCs in an in vivo mouse model. MAIT cells were activated by intratracheal injection of the activating MAIT cell antigen 5-amino-6-D-ribitulaminouracil/ methylglyoxal (5-A-RU/MeG). This activation of MAIT cells led to migration of DCs from the lung to the mediastinal lymph node (medLN) as well as DC maturation in an MR1-dependent manner. Furthermore, production of the chemokines CCL17 and CCL22 was induced by MAIT cell activation, which suggests that MAIT cells are able to modulate the immune system far more than previously thought. The possible role of MAIT cell induced DC maturation on initiation of a CD8+ T cell response is analyzed within the second result chapter. No enhanced antigen-specific CD8+ T cell response to the model antigen ovalbumin (OVA) was observed by additional MAIT cell activation.
Besides MAIT cells, recently more MR1-reactive T cells were identified. By using antigen-loaded MR1 tetramers, a population of FOXP3+ T-bet+ T cells was identified in human thymus that can bind to MR1 tetramers. In the third chapter this FOXP3+ T-bet+ T cell population was further characterized by analysis of their phenotype as well as their TCR usage. The results in this chapter will serve as a basis for further investigation of the diversity of MR1-recognition within the T cell pool.
In conclusion, this thesis reveals a new role of MAIT cells that may be used to manipulate their functions to treat different diseases like autoimmune diseases or cancer. Moreover, the knowledge of MR1-reactive T cell diversity is extended including a potential regulatory role of MR1-reactive T cells and MAIT cells. In summary, this thesis extends the current knowledge of MAIT cell biology.},

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