The road to residency Uncovering the proteome, metabolism and transcriptional networks of tissue-resident memory T cells

CD8⁺ memory T cells persist after infection as circulating and resident subsets to increase the capacity of the immune system to eradicate viruses and other intracellular pathogens upon secondary encounter. The ability of memory CD8⁺ T cells to retain their proliferative potential and to differentiate into effectors are characteristics that can be exploited for their in vitro expansion into advanced medicinal cell-based products for adoptive T cell therapies. Improving T cell centered immunotherapy requires more knowledge regarding the differentiation potential, metabolic wiring and transcriptional regulation of distinct subsets of memory T cells. Therefore, in this thesis, we explored the in vivo and in vitro reactivation of circulating and resident memory CD8⁺ T populations and focused on their differentiation pathways, relevant environmental cues, and important metabolic and transcriptional regulators.