CD8α-11b+ dendritic cells but not CD8α+ dendritic cells mediate cross-tolerance toward intestinal antigens

Cross-presentation is a critical process by which antigen is displayed to CD8 T cells to induce tolerance. It is believed that CD8 alpha(+) dendritic cells (DCs) are responsible for cross-presentation, suggesting that the CD8 alpha(+) DC population is capable of inducing both cross-priming and cross-tolerance to antigen. We found that cross-tolerance against intestinal soluble antigen was abrogated in C57BL/6 mice lacking mesenteric lymph nodes (MLNs) and Payer patches (PPs), whereas mice lacking PPs alone were capable of developing CD8 T-cell tolerance. CD8 alpha(-)CD11b(+) DCs but not CD8 alpha(+) DCs in the MLNs present intestinal antigens to relevant CD8 T cells, while CD8 alpha(+) DCs but not CD8 alpha(-)CD11b(+) DCs in the spleen exclusively cross-present intravenous soluble antigen. Thus, CD8 alpha(-)CD11b(+) DCs in the MLNs play a critical role for induction of crosstolerance to dietary proteins.