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 events involved in HIV primary infection. In the past year, we have published four papers on this topic and have one paper in press. Firstly, we investigated and reported on the role of cytokines in the regulation of HIV co-receptor expression and subsequent HIV infection in LC. We found that type 1 cytokines (e.g., IFNg) decreased expression of CXCR4 on LC and reduced subsequent infection of CXCR4-using HIV, whereas type 2 cytokines (e.g., IL-4) induced the opposite outcome. This was followed by a study where we determined the effects of HIV and human herpesvirus 6 (a purported co-factor involved in the pathogenesis of AIDS) in co- infected DC cultures; human herpesvirus 6 led to a marked decrease in HIV replication in co-infected cells. Very recently, we collaborated with Gene Shearers group on a project where we examined the immunologic function and chemokine production of monocyte-derived DC isolated from HIV-infected individuals. DC production of chemokines and cytokines, as well as T cell stimulatory capacity, were equivalent in HIV-infected versus uninfected persons, indicating that these cells could be used to enhance immune responses in future DC-based immunotherapeutic protocols. Currently, we are preparing to submit several manuscripts that describe novel models for various aspects of sexual HIV transmission. In one, we have used normal human skin explants to pre- clinically test potential topical microbicides designed to block transmission of HIV; the second model uses a combination of skin- derived LC and human tonsils to study events involved in transmission of HIV from LC to lymphoid tissue; in the third model, we have studied HIV infection of normal human vaginal mucosal LC in collaboration with the NIH gynecologist Larry Nelson. Finally, we have recently been able to identify and characterize single LC and DC infected with HIV using intracellular p24 monoclonal antibody staining and flow cytometry. This advance has allowed us to study more precisely the phenotype and immunologic function of HIV-infected DC.100% AIDS-RELATED - HIV, Langerhans cells, dendritic cells, chemokines, cytokines, - Human Subjects & Human Tissues, Fluids, Cells, etc.
