Distinct dendritic cell subsets differentially regulate the class of immune responseinvivo

Male Mice, Inbred BALB C Lymphoid Tissue T-Lymphocytes Granulocyte-Macrophage Colony-Stimulating Factor Membrane Proteins Bone Marrow Cells CHO Cells Dendritic Cells Mice, SCID Flow Cytometry Adoptive Transfer Recombinant Proteins 3. Good health Mice, Inbred C57BL Mice 03 medical and health sciences 0302 clinical medicine Species Specificity Cricetinae Animals Humans Crosses, Genetic
DOI: 10.1073/pnas.96.3.1036 Publication Date: 2002-07-26T14:32:33Z
ABSTRACT
Dendritic cells (DCs) are unique in their ability to stimulate T cells and initiate adaptive immunity. Injection of mice with the cytokine Flt3-ligand (FL) dramatically expands mature lymphoid and myeloid-related DC subsets. In contrast, injection of a polyethylene glycol-modified form of granulocyte/macrophage colony-stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset. These DC subsets differ in the cytokine profiles they induce in T cellsin vivo. The lymphoid-related subset induces high levels of the Th1 cytokines interferon γ and interleukin (IL)-2 but little or no Th2 cytokines. In contrast, the myeloid-related subset induces large amounts of the Th2 cytokines IL-4 and IL-10, in addition to interferon γ and IL-2. FL- or GM-CSF-treated mice injected with soluble ovalbumin display dramatic increases in antigen-specific antibody titers, but the isotype profiles seem critically dependent on the cytokine used. Although FL treatment induces up to a 10,000-fold increase in ovalbumin-specific IgG2a and a more modest increase in IgG1 titers, GM-CSF treatment favors a predominantly IgG1 response with little increase in IgG2a levels. These data suggest that distinct DC subsets have strikingly different influences on the type of immune response generatedin vivoand may thus be targets for pharmacological intervention.
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