Conventional/Classical Dendritic Cells

Conventional or classical dendritic cells (cDCs) have a characteristic morphology defined by long dendrite extensions and high MHC class II expression. Although there appears to be functional homology between mouse and human cDCs, these cells express unique, species-specific markers. Mouse lymphoid tissue-resident cDCs are found in the thymus, spleen, lymph nodes, and Peyer’s patches. These cells are either CD8 alpha⁺ or CD11b⁺. Mouse CD8 alpha⁺ cDCs are recognized for their ability to cross-present extracellular antigens to CD8⁺ T cells, produce IL-12 and IFN-gamma upon activation, and prime Th1 and cytotoxic T cell responses. In contrast, the CD11b⁺ cDC subset preferentially activates CD4⁺ T cells and induces Th2 or Th17 differentiation. In addition to the lymphoid tissue-resident cDCs, three subsets of mouse migratory/non-lymphoid tissue cDCs have also been identified. These include CD103^-CD11b⁺ cDCs, CD103⁺CD11b^- cDCs, and CD103⁺CD11b⁺ intestinal cDCs. Migratory/non-lymphoid tissue CD11b⁺ cDCs are functionally similar to lymphoid tissue-resident CD11b⁺ cDCs, while CD103⁺ cDCs share similarities with lymphoid tissue-resident CD8 alpha⁺ cDCs, including their ability to cross-present antigens to CD8⁺ T cells.

Human cDCs are found in both lymphoid and peripheral tissues. Two subsets have been characterized that are both Lin^- (CD3^-, CD14^-, CD19^-, CD20^-, CD56^-) and either CD1c/BDCA-1⁺ or Thrombomodulin/CD141/BDCA-3⁺. Human CD1c/BDCA-1⁺ cDCs are thought to correspond to mouse lymphoid tissue-resident CD11b⁺ cDCs and share some key features including similar gene expression profiles and their ability to preferentially prime CD4⁺ T cells. In contrast, Thrombomodulin/CD141/BDCA-3⁺ cDCs act as phenotypic and functional equivalents of mouse CD8 alpha⁺ cDCs. They express the cell surface receptors, XCR1 and CLEC9A, cross-present extracellular antigens to CD8⁺ T cells, and promote Th1 differentiation and cytotoxic T lymphocyte activation.