Tissue resident T-cells (TRM) are a memory T-cell subset, which appear to be critical in the control of viral infections. TRM remain lodged in tissue long after infection is eliminated and exist in disequilibrium with T-cells that circulate in blood and lymphatic tissue. These cells are present at portals of viral entry and express an antiviral alarm upon contact with their cognate antigen. It is therefore believed that TRM are vital in establishing early containment of many viral infections.
A major challenge in the field is linking highly mechanistic observations from animal models of infection to observational data gathered from humans. In collaboration with Drs, Martin Prlic and Jennifer Lund, we seek to understand the duration and mechanisms of protection that tissue resident CD4+ and CD8+ cells provide in tissue. To accomplish this, we are employing complementary tools. We are conducting human biopsy studies to elucidate and characterize the nature of spatial tissue resident T-cell and antiviral cytokine dynamics. We also helped develop a mouse model of mucosal HSV-2 infection with the long-term goal of characterizing protective parameters of CD4+ and CD8+ T-cell density, movement and killing rate in tissue. Our experimental studies are specifically catered to inform development of realistic three-dimensional mathematical models of the infection microenvironment. The ultimate goal of this project is to identify threshold densities, as well as phenotypic characteristics that are necessary for rapid viral containment following therapeutic or prophylactic vaccination.