The goal of our project is to improve our understanding of antiviral human memory T cells, particularly how they are distributed and function in different tissues. We have made significant progress in our research.
First, we aimed to create a detailed map of virus-specific CD8+ T cells throughout the human body. To do this, we developed advanced single-cell technologies and data analysis tools. We also set up a program to collect and study paired organ samples from well-characterized donors, allowing us to trace individual T cell clones across various tissues. This effort has given us a detailed view of where these cells are located and how they function.
We have further developed methods to detect memory T cell responses to 32 different viruses from a single sample. We identified a set of viral targets and are producing special reagents to identify these for single-cell sequencing. We have recruited nearly 50 organ donors and collected a wide range of tissue samples. Our technical processes for analyzing these samples are fully operational. A pilot study focusing on T cell responses to viruses like CMV, EBV, flu, and SARS-CoV-2 has provided significant insights into the diversity and behavior of these antiviral T cells. Notably, we have published findings on T cell immunity to SARS-CoV-2, including how these T cells recognize viral variants and form unique functional characteristics after vaccination versus infection.
Second, we focused on understanding if different types of virus-specific CD8+ T cells have unique functions in various tissues. Our preliminary data showed that tissue-resident memory T cells (TRMs) can be categorized based on specific markers like CD127. We found that CD8+ T cell killing ability varies by tissue location and viral target. Using various models, we demonstrated that certain environmental cues could influence the expression of killing molecules in these cells.
Finally, we are investigating how the local tissue environment shapes the genetic and functional properties of these T cells. We have started developing organoid models and single-cell techniques to initiate studies of the genetic landscape of these T cells. These organoid models help us understand how the local environment influences T cell behavior.
Overall, we have made substantial progress in setting up the technical infrastructure, recruiting organ donors, and analyzing the collected data. Our work continues to refine methods and expand analyses, aiming to achieve the project's goals and contribute significantly to understanding human immunity.
