Dendritic cells (DC) are able to capture, process, and present exogenous Ag to CD8+ T lymphocytes through MHC class I, a process referred to as cross-presentation. In this study, we demonstrate that CD103+(CD11c high CD11b low) and CD103−(CD11c int CD11b high) DC residing in the lung-draining bronchial lymph node (brLN) have evolved to acquire opposing functions in presenting innocuous inhaled Ag. Thus, under tolerogenic conditions, CD103− DC are specialized in presenting innocuous Ag to CD4+ T cells, whereas CD103+ DC, which do not express CD8α, are specialized in presenting Ag exclusively to CD8+ T cells. In CCR7-deficient but not in plt/plt mice, Ag-carrying CD103+ DC are largely absent in the brLN, although CD103+ DC are present in the lung of CCR7-deficient mice. As a consequence, adoptively transferred CD8+ T cells can be activated under tolerizing conditions in plt/plt but not in CCR7-deficient mice. These data reveal that CD103+ brLN DC are specialized in cross-presenting innocuous inhaled Ag in vivo. Because these cells are largely absent in CCR7−/− mice, our findings strongly suggest that brLN CD103+ DC are lung-derived and that expression of CCR7 is required for their migration from the lung into its draining lymph node.