Drexel University College of Medicine

Microbiology and Immunology Graduate Program B.A. – Biology, Drew University, Madison, NJ Email: kpe23@drexel.edu Advisor: Dr. Stephen Jennings

Thesis Research Summary:

My research is focused on the role of herpes simplex virus type 1 (HSV-1)-specific CD8-T cells in contributing to the maintenance of HSV-1 latency in sensory neurons. These virus specific effector cells are actively engaged with latently infected neurons, forming immunological synapses and releasing effector molecules, which prevent viral reactivation. Stimuli that induce viral reactivation have a common effect of reducing CD8-T cell levels in the ganglia, implicating the vital role these cells play in maintaining latency. There is emerging evidence that these cells could belong to a novel class of memory cells based upon their peculiar homing patterns. Distinct from Central memory T cells and Effector memory T cells, Tissue resident memory T cells (Trm) are retained in tissue locations of prior antigen exposure for long periods of time. These cells down regulate homing receptors to regional lymph nodes and upregulate integrin receptors that allow them to remain in the tissue they were seeded into. Their role in viral disease is one of rapid response upon re-exposure to antigen. Effector memory T cells, although antigen specific and capable of rapid effector molecule release, migrate through various tissues and may not reside in a tissue location where infection has occurred previously or a location capable of supporting infection. Trm cells, however, reside in tissue compartments where infection has already occurred and thus are capable of supporting infection upon re-exposure. Rapid effector molecule release can reduce the extent of infection by rapidly inducing an immune response and clearing out infectious agents. The CD8-T cells in latently infected ganglia have similar homing patterns to Trm cells described in other tissues. These cells do not migrate out of the ganglia in response to homing signals, have very low homeostatic turnover, and are not repopulated from circulating CD8-T cells.  Further characterization of the expression profiles of molecules associated with CD8-T cell trafficking are required to confirm that CD8-T cells surrounding latently infected neurons do, in fact, belong to this novel class of immunologic memory cells.  These studies will contribute to an understanding of the activation processes involved in the generation of the Trm subpopulation, and approaches to be taken to optimize their generation during the immune response to HSV-1.