Probing Dendritic Cell Function by Guiding the Differentiation of Embryonic Stem Cells

Abstract

Publisher Summary Dendritic cells (DC) are unique among the populations of antigen presenting cells by virtue of their capacity to direct the outcome of antigen recognition by naive T cells. By serving as messengers direct from the site of infection, DC inspect the T cell repertoire, identifying those cells specific for the cargo of antigens they display on their surface as peptide-MHC complexes. Having encountered T cells with a complementary receptor for antigen, DC deliver instructions directing the expansion of relevant clones and their deployment to the front line of the immune response. Should these T cells pose a threat to the integrity of the host, DC may decommission them from active service, thereby minimizing any damage from friendly fire. The role played by DC in fine-tuning these opposing forces of self-tolerance and immunity makes them attractive candidates for immune intervention in a variety of disease states. Alternatively, by specifically enhancing their immunogenicity, DC might be coerced into breaking the natural state of self-tolerance to tumor-associated antigens (TAA) and directing the full force of the immune response towards transformed cells and established tumors. Despite their clinical potential, very little is known of the molecular basis of DC function, which permits them to fulfill these conflicting roles. An approach has been developed to the study of DC, which draws on the unique features of embryonic stem (ES) cells: their self-renewal, pluripotency, and tractability for genetic modification. This chapter describes in detail the protocols involved and discusses the advantages such an experimental system provides over the current art.