Identification of CD68+lin- peripheral blood cells with dendritic precursor characteristics.
Expression of CD68 (macrosialin) in the absence of surface and lysosomal lineage marker molecules is a characteristic feature of T zone-associated plasmacytoid monocytes, which were recently shown to represent precursors of dendritic cells (DC). We demonstrate here a minor population of strongly CD68-positive (CD68bright) blood cells that lack all analyzed myeloid surface (CD14-, CD33-, CD13-, CD11b-, CD11c-) and lysosomal (myeloperoxidase, MPO- and lysozyme, LZ-) marker molecules (0.4 +/- 2% of the total mononuclear cells). These CD68bright, lineage marker-negative (lin-) cells can be induced to proliferate in the presence of IL-3. They do not acquire myeloid features even upon stimulation with granulocyte-macrophage CSF plus IL-1, IL-3, and IL-6. Instead, these cells develop typical DC characteristics upon culture. Furthermore, these CD68brightlin- DC precursors acquire mature DC characteristics (CD86+, CD83+, CD54bright) upon stimulation with CD40 ligand plus IL-3. A second subset of DC precursor-like blood cells was found to weakly express CD68 (0.3 +/- 0.2% of the total mononuclear cells) and to coexpress several myeloid lineage associated molecules (LZ+, CD11c+, CD33+, CD13+). Cells of this second subset resemble both previously described myeloid-related peripheral blood DC and germinal center DC. Analysis of peripheral blood leukocytes for CD68 thus revealed the existence of two cell subsets that phenotypically resemble lymphoid tissue-associated DC. The unique phenotype CD68brightlin- is highly reminiscent of T zone-associated plasmacytoid monocytes. CD68brightlin- blood leukocytes also functionally resemble plasmacytoid monocytes. The lack of all analyzed myeloid features by CD68brightlin- blood leukocytes suggests that these cells arise from a novel nonmyeloid human DC differentiation pathway.
Institute of Immunology, Vienna International Research Cooperation Center, Novartis Forschungsinstitut, University of Vienna, Austria. herbert.strobl@univie.ac.at
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H
Strobl
C
C
Scheinecker
E
E
Riedl
B
B
Csmarits
C
C
Bello-Fernandez
W F
WF
Pickl
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Majdic
W
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Knapp
D015703:Antigens, CD / Q000096:biosynthesis*; D018952:Antigens, CD34 / Q000096:biosynthesis; D019011:Antigens, CD7 / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D018845:CD11 Antigens / Q000096:biosynthesis; D018826:CD13 Antigens / Q000096:biosynthesis; D015704:CD4 Antigens / Q000096:biosynthesis; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand; D018956:CD5 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D063268:Sialic Acid Binding Ig-like Lectin 3; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D000097802:CD83 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D018952:Antigens, CD34; D019011:Antigens, CD7; D015214:Antigens, Differentiation, Myelomonocytic; D018845:CD11 Antigens; D018826:CD13 Antigens; D015704:CD4 Antigens; D019013:CD40 Antigens; D023201:CD40 Ligand; D018956:CD5 Antigens; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D017493:Leukocyte Common Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D000097802:CD83 Antigen; C571163:CD33 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule