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Eliciting Cytotoxic T-lymphocyte Responses to HIV by Human Dendrocyte in vitro T-cell Activation with Synthetic Peptide-containing Microspheres

Eliciting Cytotoxic T-Lymphocyte Responses to HIV by Human Dendritic Cell Driven in vitro T-Cell Activation with Synthetic Peptide-Containing Microspheres

Killingbeck S, Immunity Project, UC Berkeley School of Public Health; Zompi S, Immunity Project, University of California San Francisco School of Medicine; Paranjpe V, Immunity Project; Patel R, Immunity Project; Hoban H, Immunity Project; McLoughlin S, Immunity Project; Lloyd P, Immunity Project; Rouskey CJ, Immunity Project; Herst CV, Immunity Project; Harris PE, Immunity Project, Columbia Department of Medicine at the College of Physicians and Surgeons; Rubsamen R, Immunity Project, Massachusetts General Hospital

We describe an in vitro assay that uses poly-lactide-co-glycolide (PLGA) microparticles containing a model HIV-1 CTL epitope to pulse monocyte derived dendritic cells (MDDC) and subsequently prime autologous CD8+ T cell effector function in vitro.  We demonstrate that microparticle-primed MDDC are capable of activating, priming and expanding epitope-specific CD8+ T cells that have the capacity to kill autologous HIV-1 infected CD4 Target cells and suppress p24 antigen in effector:target co-cultures.  These studies reveal the potential of such a delivery mechanism as a vaccination method that targets dendritic cells in vivo.