Thesis defense Loreto Parga Vidal

On 8 October 2021 Loreto Parga Vidal defended her thesis 'Embarking on a journey: Generation, maintenance and reactivation of tissue-resident memory T cells' at the University of Amsterdam

Promotor
Prof RAW van Lier MD PhD
Copromotor
KPJM van Gisbergen PhD

Venue
Agnietenkapel, Universiteit van Amsterdam

Summary

Our immune system has evolved over the years to endow us with optimal protection against a wide range of invading pathogens on a daily basis. Immunological memory is a key factor in the success of the immune system and it relies on the complementary action of memory CD8⁺ T cells, memory CD4⁺ T cells and B cells. Three memory CD8⁺ T cell subsets have been defined based on their trafficking properties and specific functions: central memory (T_CM), effector memory (T_EM) and tissue-resident memory (T_RM) T cells. In contrast to T_CM and T_EM, T_RM do not recirculate and they permanently reside in peripheral tissues where they act as sentinels that can quickly engage effector functions upon local reinfection. Importantly, multiple studies have shown the superior capacity of T_RM to provide local protection against pathogens and tumors.
Given their importance in protection against reinfection, unraveling the specific features of T_RM appears highly relevant to improve T cell-targeted immunotherapeutic approaches. To develop T_RM for therapy, it is essential to understand how T_RM arise within the T cell population after primary infection and how they respond upon pathogen re-encounter to clear the secondary infection. Thus, in this thesis, we aimed to elucidate the mechanisms governing T_RM biology: from early development upon pathogen encounter, to their interaction with the microenvironment during maintenance, and to their reactivation during secondary responses. Our findings provide a solid framework of the cellular and molecular mechanisms underlying the journey of a T_RM during infection.