Table of Contents
Table of illustrations...2
Abbreviations...5
Summary - Résumé...15
Foreword...19
Introduction...25
1. Transcriptional and epigenetic control of naïve CD8+ T cell development...26
1.1From the bone marrow to the thymus...26
1.2 Intra-thymic development...29
1.3 Thymic egress, post-thymic maturation, and entry in the long-lived naïve CD8+ T cell pool...44
2. The rise of effector and memory CD8+ T cells in the context of primary antigenic challenge...52
2.1 CD8+ T cell trafficking, T cell receptor signaling, co-stimulatory signals and inflammatory cytokines during primary Ag encounter...54
2.2 Transcriptional and epigenetic control of terminal effector versus conventional memory precursor CD8+ T cell fate during primary Ag encounter...60
3. Specialization, maintenance and re-challenge of Ag-specific conventional memory CD8+ T cells...85
3.1 Transcriptional and epigenetic control underlying the trafficking, specialization, and maintenance of long-lived Ag-specific conventional memory CD8+ T cell subsets...85
3.2 Re-challenge of Ag-specific conventional memory CD8+ T cells...99
3.2.1 Nature and epigenetic maintenance of the effector potential of conventional memory CD8+ T cells...99
3.2.2 Ag-specific and bystander aspects of conventional memory CD8+ T cells during secondary challenge...103
4. Development and functions of unconventional memory CD8+ T cell subsets...109
4.1 Unconventional memory CD8+ T cells in lymphodeplete conditions...109
4.2 Unconventional memory CD8+ T cells in lymphoreplete conditions...111
4.2.1 TIM cells...111
4.2.2 TVM cells...116
Aim of the study...127
Experimental Section - Results...129
Discussion...161
1. What the transcriptional signature and epigenetic landscape of TIM cells teach us about conventional memory formation and functions...163
2. How EOMES and its partners shape CD8+ T cell fate through epigenetic reprogramming...178
3. Perspectives and concluding remarks...196
References...199
