PMID- 9927689 OWN - NLM STAT- MEDLINE DCOM- 19990305 LR - 20230331 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 96 IP - 3 DP - 1999 Feb 2 TI - Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. PG - 1036-41 AB - 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 cells in vivo. The lymphoid-related subset induces high levels of the Th1 cytokines interferon gamma 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 gamma 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 generated in vivo and may thus be targets for pharmacological intervention. FAU - Pulendran, B AU - Pulendran B AD - Immunex Corporation, 51 University Street, Seattle, WA 98101, USA. FAU - Smith, J L AU - Smith JL FAU - Caspary, G AU - Caspary G FAU - Brasel, K AU - Brasel K FAU - Pettit, D AU - Pettit D FAU - Maraskovsky, E AU - Maraskovsky E FAU - Maliszewski, C R AU - Maliszewski CR LA - eng PT - Journal Article PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Membrane Proteins) RN - 0 (Recombinant Proteins) RN - 0 (flt3 ligand protein) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Adoptive Transfer MH - Animals MH - Bone Marrow Cells/cytology/immunology MH - CHO Cells MH - Cricetinae MH - Crosses, Genetic MH - Dendritic Cells/classification/drug effects/*immunology MH - Flow Cytometry MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - Lymphoid Tissue/cytology/immunology MH - Male MH - Membrane Proteins/*immunology/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, SCID MH - Recombinant Proteins/immunology/pharmacology MH - Species Specificity MH - T-Lymphocytes/immunology PMC - PMC15346 EDAT- 1999/02/03 00:00 MHDA- 1999/02/03 00:01 PMCR- 1999/08/02 CRDT- 1999/02/03 00:00 PHST- 1999/02/03 00:00 [pubmed] PHST- 1999/02/03 00:01 [medline] PHST- 1999/02/03 00:00 [entrez] PHST- 1999/08/02 00:00 [pmc-release] AID - 4617 [pii] AID - 10.1073/pnas.96.3.1036 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1036-41. doi: 10.1073/pnas.96.3.1036.