Identification of CD68+lin- Peripheral Blood Cells with Dendritic Precursor Characteristics

• Published in: The Journal of immunology (1950) 1998-07, Vol.161 (2), p.740-748
• Main Authors: Strobl, Herbert, Scheinecker, Clemens, Riedl, Elisabeth, Csmarits, Bettina, Bello-Fernandez, Concha, Pickl, Winfried F, Majdic, Otto, Knapp, Walter
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Antigens, CD34 - biosynthesis; Antigens, CD7 - biosynthesis; Antigens, Differentiation, Myelomonocytic - biosynthesis; CD11 Antigens - biosynthesis; CD13 Antigens - biosynthesis; CD4 Antigens - biosynthesis; CD40 Antigens - immunology; CD40 Antigens - metabolism; CD40 Ligand; CD5 Antigens - biosynthesis; CD83 Antigen; Cell Differentiation - immunology; Cell Division - immunology; Cell Separation; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Granulocytes - cytology; HLA-DR Antigens - biosynthesis; Humans; Immunoglobulins - biosynthesis; Immunophenotyping; Leukocyte Common Antigens - biosynthesis; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Ligands; Lymphocyte Activation; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Monocytes - cytology; Sialic Acid Binding Ig-like Lectin 3; Stem Cells - cytology; Stem Cells - immunology; Stem Cells - metabolism; T-Lymphocytes - immunology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.2.740

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.