PMID- 10861097 OWN - NLM STAT- MEDLINE DCOM- 20000731 LR - 20190515 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 165 IP - 1 DP - 2000 Jul 1 TI - Flt3-ligand and granulocyte colony-stimulating factor mobilize distinct human dendritic cell subsets in vivo. PG - 566-72 AB - Dendritic cells (DCs) have a unique ability to stimulate naive T cells. Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and in vivo. In humans, the monocyte-derived CD11c+ DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11c- plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines. In this paper we report that administration of either Flt3-ligand (FL) or G-CSF to healthy human volunteers dramatically increases distinct DC subsets, or DC precursors, in the blood. FL increases both the CD11c+ DC subset (48-fold) and the CD11c- IL-3R+ DC precursors (13-fold). In contrast, G-CSF only increases the CD11c- precursors (>7-fold). Freshly sorted CD11c+ but not CD11c- cells stimulate CD4+ T cells in an allogeneic MLR, whereas only the CD11c- cells can be induced to secrete high levels of IFN-alpha, in response to influenza virus. CD11c+ and CD11c- cells can mature in vitro with GM-CSF + TNF-alpha or with IL-3 + CD40 ligand, respectively. These two subsets up-regulate MHC class II costimulatory molecules as well as the DC maturation marker DC-lysosome-associated membrane protein, and they stimulate naive, allogeneic CD4+ T cells efficiently. These two DC subsets elicit distinct cytokine profiles in CD4+ T cells, with the CD11c- subset inducing higher levels of the Th2 cytokine IL-10. The differential mobilization of distinct DC subsets or DC precursors by in vivo administration of FL and G-CSF offers a novel strategy to manipulate immune responses in humans. FAU - Pulendran, B AU - Pulendran B AD - Baylor Institute for Immunology Research, Dallas, TX 75204, USA. FAU - Banchereau, J AU - Banchereau J FAU - Burkeholder, S AU - Burkeholder S FAU - Kraus, E AU - Kraus E FAU - Guinet, E AU - Guinet E FAU - Chalouni, C AU - Chalouni C FAU - Caron, D AU - Caron D FAU - Maliszewski, C AU - Maliszewski C FAU - Davoust, J AU - Davoust J FAU - Fay, J AU - Fay J FAU - Palucka, K AU - Palucka K LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adjuvants, Immunologic) RN - 0 (Cytokines) RN - 0 (Integrin alphaXbeta2) RN - 0 (Interferon-alpha) RN - 0 (Ligands) RN - 0 (Membrane Proteins) RN - 0 (flt3 ligand protein) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM MH - Adjuvants, Immunologic/*administration & dosage/*physiology MH - Adult MH - CD4-Positive T-Lymphocytes/immunology MH - Cell Differentiation/immunology MH - Cytokines/biosynthesis MH - Dendritic Cells/cytology/*immunology/metabolism MH - Fetal Blood/cytology MH - Granulocyte Colony-Stimulating Factor/*administration & dosage/*physiology MH - Hematopoietic Stem Cells/immunology/metabolism MH - Humans MH - Injections, Subcutaneous MH - Integrin alphaXbeta2/biosynthesis MH - Interferon-alpha/biosynthesis MH - Ligands MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed MH - *Membrane Proteins/*administration & dosage/*physiology MH - T-Lymphocyte Subsets/immunology/metabolism EDAT- 2000/06/22 10:00 MHDA- 2000/08/06 11:00 CRDT- 2000/06/22 10:00 PHST- 2000/06/22 10:00 [pubmed] PHST- 2000/08/06 11:00 [medline] PHST- 2000/06/22 10:00 [entrez] AID - ji_v165n1p566 [pii] AID - 10.4049/jimmunol.165.1.566 [doi] PST - ppublish SO - J Immunol. 2000 Jul 1;165(1):566-72. doi: 10.4049/jimmunol.165.1.566.