Dissecting tissue-resident memory T cell heterogeneity in human tissues

Despite the extraordinary advances in medicine over the last few decades, infectious disease remains among the leading causes of morbidity and mortality worldwide. Our understanding of how protective immune responses can be generated and augmented by vaccines or immunotherapies are therefore of prime importance for improving human health. Recent studies have identified a heterogeneous population of non-circulating memory T cells, known as tissue-resident memory T cells (TRM), that are distributed in mucosal/barrier sites and are essential in mediating protective immunity during infection and after vaccination. However, due to the difficulty of studying immune cells directly in human tissues, basic questions of how TRM function and how they differ across multiple tissues within the same individual remain unanswered. My research will utilize a unique human tissue resource in which multiple mucosal and lymphoid organs are obtained from research-consented organ donors in order to dissect the similarities and differences between TRM subsets across tissue sites. I will use a combination of cutting-edge techniques including high-dimensional immune profiling, multi-parameter imaging, and single cell transcriptomic approaches to generate a "human atlas" of TRM phenotype and function throughout the human body. With this investigation, my objective is to define and characterize TRM identity and function using a one-of-a-kind tissue resource that allows unprecedented access to study human tissue immunity. Understanding how TRM function in humans is central to the design of new vaccines and immunotherapies aimed at boosting tissue immunity, with the ultimate goal reducing deaths from infectious disease.