Langerhans cells (LC) are members of the dendritic cell (DC) family and function as the major antigen presenting cells of epidermis and genital mucosal surfaces. It is generally believed that LC are the initial target cells for HIV following mucosal exposure to virus. My lab is focused on studying how HIV interacts with LC and other DC, with the hope that this work will add insight into the early biologic events involved in HIV primary infection. In the past year, we have published a report that documents HIV transmission from LC to lymphoid tissue, using a unique ex vivo tissue culture model for this study. In addition, we currently have a paper in review that describes another novel ex vivo tissue model of HIV transmission. We have used this model to identify, quantify, and phenotype individually infected LC. Furthermore, we have shown that LC infection can be blocked by pre-incubation of tissue with potential microbicidal agents. Microbicides are drugs being developed for topical use to prevent sexual transmission of HIV. Thus, with our studies, we have provided important pre-clinical information in the development of such compounds. Currently, we are preparing to submit several other manuscripts: 1) in a third ex vivo model, we have studied HIV infection of normal human vaginal mucosal LC in collaboration with the NIH gynecologist Larry Nelson; and 2) we have recently been able to identify and immunologically characterize in detail single DC infected with HIV using intracellular p24 monoclonal antibody staining and flow cytometry. Taken together, this work has contributed greatly to further understanding the biologic events involved in sexual transmission of HIV. In particular, much of these studies rely on unique ex vivo tissue systems that we have developed and that offer considerable advantage over standard single cell culture experiments. 100% AIDS-RELATED
