Effects of Herpes Simplex Virus on cutaneous γδ T Cells in Mice and Men

γδT cells are a rare population of T cells predominantly identified in mucoepithelial tissues including the skin that modulate both innate and adaptive responses. Herpes simplex virus (HSV) is a medically important pathogen that often initially enters through the skin. In this thesis, I first observed that HSV productively infects epidermal γδT cells by detecting de novo viral gene transcription in vitro, providing the first evidence that epidermal γδT cells are important for the transmission of HSV. Using a flank infection model of HSV, I demonstrate that the presence of γδT cells in the murine skin is associated with increased severity of herpetic lesions, increased inflammation and increased spread of infectious HSV-1 to the ganglia and the site of recurrent infection, probably due to a weaker IFN-γ response at the primary site of infection. Epidermal and dermal γδT cells also have distinct roles during flank HSV infection of mice. Epidermal γδT cells regulate T cell effector function at the primary site and dermal γδT cells contribute to the subsequent viral inflammation and pathogenesis of recurrent herpetic lesions at the secondary site. Using human surgical skin explants, I observe that γδT cells are attracted towards the epidermis during early HSV infection then are gradually attracted towards the deep dermis during late infection, probably driven by chemoattractants mediated by neutrophils and/or chemokines such as CCL2/MCP1. γδT cells in the HSV infected human skin appeared to have close interactions with LCs, neutrophils, and IL-17 producing cells, suggesting these cells may interact to contribute to the downstream immunological effects. Taken together, I highlight the importance of γδT cells in the immune response to HSV infection in both mice and humans, leading to a potential augment to the therapeutic or vaccination strategies against diseases related to HSV and other viruses