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Localization of Myeloid Dendritic Cells in the Mouse Peyer's Patch Frozen sections of Peyer's patches were doubly stained with antibodies against CD11c (green) in combination with anti-CD11b (red). The yellow cells in the dome region represent the myeloid dendritic cells. The red cells in the villus lamina propria are macrophages and neutrophils, whereas the green cells in the dome and in the interfollicular region are the double-negative dendritic cells.

Previously, we have characterized three major populations of DCs in the Peyer's patches, which are the primary immune inductive organ in the gastrointestinal mucosa. The three DC populations reside in distinct anatomical locations within the Peyer's patch, and secrete distinct sets of cytokines and influence T helper cells to differentiate into either Th1 or Th2 cell types (see the diagram below). The first type of DCs, called myeloid DCs (CD11b⁺), reside in the subepithelial dome just underneath the follicle-associated epithelium. The myeloid DCs of the Peyer's patch are special compared to their counterpart in other lymphoid organs in that they have the ability to secrete high levels of IL-10 (not IL-12) and induce IL-4 and IL-10 secretion from CD4⁺T cells. These cells localize in the subepithelial dome region by responding to the chemokine MIP-3 secreted from the follicle-associated epithelium. The second type of DCs, lymphoid DCs (CD8+), localize exclusively in the interfollicular region. This area contains most of the T cells in the Peyer's patch, and DCs can be seen in close proximity with T cells. The lymphoid DCs localize in the T cell region by responding to the chemokines MIP-3ß and SLC. Finally, we have identified a new subset of DCs called double negative (DN) DCs. These cells lack the expression of both lymphoid (CD8) and myeloid (CD11b) markers and they are localized in the subepithelial dome, interfollicular region and in the epithelium. These DN intraepithelial DCs are found in close contact with M cells, which are specialized in taking up luminal antigens into the dome region. Both the DN and lymphoid DCs secrete IL-12 and influence naïve T cells to become Th1 effector cells.

Our goal is to define the mechanisms of T cell priming within the Peyer's patch following infection by naturally occurring intestinal pathogen such as Salmonella typhimurium. This infection is characterized by the differentiation of Th1 cells, and the protection observed is conferred by IFN-mediated mechanism. Specifically, we would like to understand how the three dendritic cell subsets in the Peyer's patch induce such effector T cells, and where the initiating events are taking place in vivo.

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  Last modified: August 17, 2002.




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