Plasmacytoid Dendritic Cells (pDC) are a minor population of circulating immune cells (0.1 - 0.5% of Peripheral Blood Mononuclear Cells), but are critical in the initiation of host antiviral immunity. Through secretion of type I interferon (IFN) and the stimulation of lymphocytes, pDCs effectively branch the innate and adaptive immune cell responses. Despite pDCs central role in host antiviral immune response, infection by Human Immunodeficiency Virus (HIV) is correlated with diminished circulating pDC number and a reduced capacity to secrete IFNα, a type I IFN. Fortunately, since the mid 1990’s HIV patients are treated with a combination of anti-viral drugs termed “Highly Active Anti-Retroviral Therapy” (HAART) which is very effective at reducing viral load and enabling immune cell restoration. Though HAART is effective at reducing viral replication, it does not treat all the symptoms of HIV infection (e.g. HIV related wasting). Consequently, HIV patients that have been successfully treated by HAART will often turn to medicinal cannabinoids, such as Dronabinol (synthetic Δ9-Tetrahydrocannabinol – THC), for both the orexigenic and anxiolytic effects. However, THC is a well-characterized immunosuppressant, known to cause exacerbation of bacterial and viral infections. In my research the role of THC-mediated suppression of TLR-dependent pDC activation and subsequent pDC dependent T cell stimulation will be evaluated in HIV+ and HIV- human donors. Overall, the findings from this study will facilitate a greater understanding of the immunomodulatory effects and potential differences cannabinoid based therapies have in HIV- and HIV+ patient populations.