Dendritic Cells Promote Th Proliferation Th Polarization, whereas Conventional Monocyte-Derived Dendritic Cells Promote

Monocyte-derived dendritic cells (moDCs) dramatically increase in numbers upon infection and inflammation; accordingly, we found that this also occurs during allogeneic responses. Despite their prominence, how emergent moDCs and resident conventional DCs (cDCs) divide their labor as APCs remain undefined. Hence, we compared both direct and indirect presentation by murine moDCs versus cDCs. We found that, despite having equivalent MHC class II expression and in vitro survival, moDCs were 20-fold less efficient than cDCs at inducing CD4 + T cell proliferation through both direct and indirect Ag presentation. Despite this, moDCs were more potent at inducing Th1 and Th17 differentiation (e.g., 8-fold higher IFN-g and 2-fold higher IL-17A in T cell cocultures), whereas cDCs induced 10-fold higher IL-2 production. Intriguingly, moDCs potently reduced the ability of cDCs to stimulate T cell proliferation in vitro and in vivo, partially through NO production. We surmise that such division of labor between moDCs and cDCs has implications for their respective roles in the immune response. D endritic cells (DCs) are heterogeneous and can be divided into subsets based on selective characteristics including appearance, location, phenotype, transcription factors, function, and ontogeny (1, 2). For example, plasmacytoid DCs have a smooth surface, are located ubiquitously, express E2-2 transcription factor, siglec-H, B220, BDCA-2, and TLR-7 and abundantly secrete type 1 IFN (3, 4), whereas CD8 + cDCs have a dendritic appearance, are located in lymphoid tissue, express ID2 and BATF3 transcription factors Clec-9A, XCR1, and TLR-3, and produce IL-12 and IFN-g. CD8 + cDCs are important in the protection against intracellular pathogens (5) and are highly efficient at cross presenting exogenous Ag on MHC class I (6), whereas CD8 2 cDCs are specialized at priming CD4 + T cells (7). Unlike other DC populations, moDCs are inconspicuous in the steady state and only become prominent during inflammation (8, 9). They are recruited from Ly6C + inflammatory monocytes via a CCR2-dependent process (8, 10, 11) and are prominent in the immune response to infections such as They have been implicated in experimental autoimmune enceph-alomyelitis (EAE) (16, 17) and in the regulation of gastrointestinal production of IgA through interactions with microflora (18). Of note, an additional, unique subset of moDCs expressing DC-specific intercellular adhesion molecule-3–grabbing nonintegrin (SIGN) has been reported to accumulate in skin-draining lymph nodes (but not in other lymph nodes or the spleen) after LPS stimulation (but not other inflammatory stimuli). These DC-SIGN–positive moDCs were found …