Flexibility of Mouse Classical and Plasmacytoid-derived Dendritic Cells in Directing T Helper Type 1 and 2 Cell Development

By A. Boonstra, C. Asselin‐Paturel, M. Gilliet, C. Crain, G. Trinchieri, Yong‐jun Liu, A. O’Garra. Journal of Experimental Medicine, 2003

658 citations recorded by the source corpus.

Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4+ T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/d53adfa0c257c27fc227abe87b25a4b2713a6ad4

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Citations in the corpus

Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen (2004, methodology): “Only when pDCs were pulsed with various doses of OVA peptide in vitro, could either Th1 or Th2 cell responses be induced (23).”
Plasmacytoid dendritic cells in immunity (2004, background): “Mouse pDCs activated in vivo with mouse cytomegalovirus and in vitro with CpG present pulsed peptides to naive T cells and induce a potent T H 1 polarization in vitro”
Dendritic-cell control of pathogen-driven T-cell polarization (2003, background): “Consequently, LPS primes for DCs that support the development of T H 1 cells, both in mice and in humans, but this T H 1-cell-inducing potential can readily be overruled in vitro by varying the experimental conditions, such as the antigen dos”
Plasmacytoid Dendritic Cells: Recent Progress and Open Questions (2011, background): “For instance, pDCs can efficiently prime CD4+ T cell responses in the lymph nodes (100), induce Th1 polarization (101, 102), and prime (103) and cross-prime”
TLR Signaling Tailors Innate Immune Responses in Human Microglia and Astrocytes1 (2005, background): “Nonetheless, the polarization of immune responses has been shown to be a complex process, and factors such as Ag dose and coreceptors may also play an important role (40, 41).”
Toll-like receptor control of the adaptive immune responses (2004, background): “Although TLR4 is expressed at low amounts on splenic DCs, freshly isolated mouse DC subsets do not respond to LPS stimulatio”