Towards the identification of the thymus seeding progenitor [Elektronische Ressource] : fate mapping of early T-cell stages using gene knock-in strategies / von Hervé Luche

INSTITUT FÜR IMMUNOLOGIE LEITER: PROF. DR. H.R. RODEWALD LEITER: PROF. DR. H.R. RODEWALD LEITER: PROF. DR. H.R. RODEWALD TOWARDS THE IDENTIFICATION OF THE THYMUS SEEDING PROGENITOR: “FATE MAPPING” OF EARLY T-CELL STAGES USING GENE “KNOCK-IN” STRATEGIES zur Erlangung des Doktorgrades Humanbiologie vorgelegt der Medizinischen Fakultät der Universität Ulm Universitätsklinikum Ulm von Hervé LUCHE aus Saint-Just en Brie, France Ulm 2007 Amtierender Dekan: Professor Dr. K.-M. DEBATIN Berichterstatter 1: Professor Dr. H.J. FEHLING Berichterstatter 2: Professor Dr. T. WIRTH Tag der Promotion: 15/06/07 À Marie et Camille CONTENTS CONTENTS I ABBREVIATIONS IV INTRODUCTION 1 1. CURRENT VIEWS IN T-CELL DEVELOPMENT 2 1.1. T-CELL PRECURSORS ARE BONE MARROW-DERIVED AND MATURE IN THE THYMUS 2 1.2. FROM BONE MARROW TO BLOOD: THE THYMUS SEEDING PROGENITOR (TSP) 8 1.3. αβ-TCR THYMOCYTE DEVELOPMENT AND IMMATURE SUBSETS 9 1.4. HETEROGENEITY OF DN1 AND EARLY T-CELL PROGENITOR (ETP) 10 341.5. DEVELOPMENT OF γδ-TCR-EXPRESSING THYMOCYTES 11 1.6. DEVENT OF THE NK-T CELL LINEAGE 12 2. PRE-TCR ALPHA-CHAIN: A GOOD MARKER FOR EARLY T-CELL DEVELOPMENT 12 2.1. THE PTα GENE AND PRE-TCR STRUCTURE 12 2.2. PTα EXPRESSION PATTERN 13 2.3. ROLE OF THE PTα CHAIN DURING αβ T-CELL DEVELOPMENT 15 2.4.