| HIV-specific CD4+ and CD8+ T lymphocytes contribute to virus suppression, but are generally unable to adequately control virus replication. Dendritic cells (DC) are professional antigen capturing and presenting cells that are able to stimulate effective immune responses both in vitro and in vivo. In HIV infection, DC-based immunotherapy has been shown to stimulate T cell responses that correlate with enhanced virus control. Several strategies are currently explored to improve these protective effects. We are currently conducting a study, for which no funding is requested here, aimed at efficient in vivo activation of HIV-1 Rev-, Tat-, and Nef-specific T cells by autologous mRNA-transfected DC in 20 antiretroviral treated patients. After treatment interruption it is expected that viral rebound will be reduced if not absent in at least some of the individuals. This offers a unique opportunity to delineate immune correlates of protection. In this project we will investigate qualitative and functional characteristics of virus-specific T lymphocytes before, during and after DC-mediated activation, including specificity, cytokine production, proliferation, cytotoxicity and antiviral capacity. The results will be correlated to in vivo virological parameters. This study will improve our understanding of immune-mediated protection against AIDS and guide future vaccine developments. |
