Anatomic location defines antigen presentation by dendritic cells to T cells in response to intravenous soluble antigens

In the spleen, exogenous antigen is preferentially presented by CD8 alpha(+)CD11b(-) DC to CD8 Tcells and by CD8 alpha(-)CD11b(+) DC to CD4 T cells. However, it is notyet clear whether the same rule applies to other secondary lymphoid organs. To address this issue, we first classified secondary lymphoid tissues into three categories based on the expression pattern of CD8 alpha and CD11b in C57BL/6 and BALB/c mice: (a) spleen, (b) mesenteric lymph node (MLN) and (c) other peripheral lvmph nodes (PLN). We then analyzed the OVA-specific T cell-stimulating capacity of each DC subset after intravenous injection with soluble OVA. Our results show that, regardless of tissue origin, CD8 alpha(-)CD11b(+) DC generally present OVA to CD4 Tcells, a finding that held true as well for CD8 alpha(+)CD11b(+) DC in PLN. In striking contrast, CD8 alpha(+)CD11b(-) DC in spleen, CD8 alpha(-)CD11b(+) DC in MLN and CD8 alpha(+)CD11b(+) DC in PLN mainly cross-present OVA to CD8 T cells in their respective tissues. Of note, CD8 alpha(-)CD11b(+) DC in MLN and CD8 alpha(+)CD11b(+) DC in PLN present OVA to both CD4 T and CD8 T cells. Therefore, the antigen-presenting capacity of each distinct DC subset is determined by its anatomic environment in combination with its surface phenotype.