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Characterization of Lymph Node Stromal Cells During Treg-Mediated Tolerance

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Characterization of Lymph Node Stromal Cells During Treg-Mediated Tolerance Characterization of lymph node stromal cells during Treg-mediated tolerance Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Maria Anna Sofia Broggi aus Mailand, Italien Basel, 2013 Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von: Prof. Dr. Ed Palmer Prof. Dr. Daniela Finke Basel, den 26. Februar 2013 Prof. Dr Jörg Schibler, Dekan Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 2.5 Schweiz“ lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licences/by-nc-nd/2.5/cheingesehen werden. 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Quelle: http://creativecommons.org/licenses/by-nc-nd/2.5/ch/ Datum: 3.4.2009 Table of contents Table of contents Table of contents ................................ ....................................................................................................... 1 Abbreviations ................................ ............................................................................................................. 5 Summary ................................ ...................................................................................................................... 9 1 Introduction ................................ ....................................................................................................... 11 1.1 The immune system ................................ ......................................................................................................... 1 1 1.1.1 Innate immunity ................................ ................................................................................................. 11 1.1.2 Adaptive immunity............................................................................................................................ 12 1.2 1.1.2.1CD4+ T T cell cells ................................ selection ................................ in the thymus ................................ ......................................................................................................................................................................... 14 13 1.2.1 T helper cells ................................ ........................................................................................................ 14 1.2.1.1 T cell migration in vivo ................................ ............................................................................................. 15 1.2.1.2 Costimulatory molecules influencing TCR signals................................ ........................................ 17 1.2.1.3 Survival and proliferation signaling in T cells ................................ ................................................ 18 1.2.2 Regulatory T cells ................................ .............................................................................................. 20 1.2.2.1 Definition, phenotype ................................ ................................................................................................ 20 1.2.2.2 Suppressive mechanism ................................ ........................................................................................... 21 1.3 1.2.2.3The lymph Regulation node ................................ of homeostasis ................................ and ................................ suppressive capacity ................................ of Treg cells ................................ ........................ 26 24 1.3.1 Lymph node stromal cells................................ .............................................................................. 27 1.3.1.1 Localization, phenotype and characterization ................................ ............................................... 27 1.3.1.2 TRCs as positive regulators of T cell responses ................................ ............................................. 29 1 Table of contents 1.4 1.3.1.3Transplantation TRCs as ................................ negative ................................ regulators of ................................ T cell responses ................................ ............................................................................................ 32 30 1.4.1 MHC restriction ................................ ................................................................................................... 32 1.4.2 Direct and indirect allorecognition ................................ ............................................................. 32 1.4.3 Different types of rejection ................................ ............................................................................ 33 1.4.4 Transplantation treatments in the clinics ................................ ............................................... 33 1.4.5 Clinical Treg cells therapy ................................ .............................................................................. 35 1.4.6 Skin transplantation ................................ .......................................................................................... 36 2 Material and Methods ................................ .................................................................................... 37 2.1 Mice ................................ ........................................................................................................................................ 37 2.2 Antibodies and reagents ................................ ............................................................................................... 37 2.3 Preparation of lymph node cells ................................ ................................................................................ 38 2.4 Sorting ................................ .................................................................................................................................. 38 2.5 Flow cytometry ................................ ................................................................................................................. 38 2.6 Skin transplantation model ................................ ......................................................................................... 39 2.7 RT-­‐PCR from cells ................................ ............................................................................................................. 39 2.8 Generation of -­‐ bone marrow derived DCs................................ .............................................................. 40 2.9 Expansion of FRC like stromal cells ex vivo ................................ .......................................................... 40 2.10 Stimulation of stromal and dendritic cells ................................ ......................................................... 41 2.11 In vitro T cell stimulation assay ................................ .............................................................................. 41 2.12 MACS separation ................................ ............................................................................................................ 41 2.13 Assessment of protein expression ................................ ........................................................................... 42 2.14 Statistical analysis ................................ ........................................................................................................ 42 2.15 Primer List ................................ ........................................................................................................................ 43 2 Table of contents 3 Aim of thesis .....................................................................................................................................
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