Cross-presentation by dendritic cells (DCs) of exogenous antigens on MHC class I is important for the generation of immune responses to intracellular pathogens, as well as for maintenance of self tolerance. In mice, the CD8(+) DC lineage is specialised for this role. However, DCs of this lineage are not born with cross-presentation capacity. Several studies have demonstrated that it must be induced as a later developmental step by cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF), or by microbial products such as toll-like receptor (TLR) ligands. Increased cross-presentation capacity is thus induced in peripheral CD8 lineage DCs during inflammation or infection. However, this capacity is already fully developed in steady-state thymic CD8(+) DCs, in accordance with their role in the deletion of self-reactive developing T cells.