Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Strobl, H; Bello-Fernandez, C; Riedl, E; Pickl, WF; Majdic, O; Lyman, SD; Knapp, W.
flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions.
Blood. 1997; 90(4):1425-1434
Doi: 10.1182/blood.V90.4.1425.1425_1425_1434
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- Führende Autor*innen der Med Uni Graz
- Strobl Herbert
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- Abstract:
- Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-beta1 (TGF-beta1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cultures of CD34+ cells supplemented with TGF-beta1, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor strongly increases both percentages (mean, 36% +/- 5% v 64% +/- 4%; P = .001) and total numbers (4.4- +/- 0.8-fold) of CD1a+ dendritic cells. These in vitro-generated CD1a+ cells molecularly closely resemble a particular type of DC known as an epidermal Langerhans cell. Generation of DC under serum-free conditions was found to strictly require supplementation of culture medium with TGF-beta1. Upon omission of TGF-beta1, percentages of CD1a+ DC decreased (to mean, 10% +/- 8%; P = .001) and, in turn, percentages of granulomonocytic cells (CD1a- cells that are lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold (P < .05). Furthermore, in the absence of TGF-beta1, FL consistently promotes generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free single-cell cultures set up under identical TGF-beta1- and FL-supplemented culture conditions showed that high percentages of CD34+ cells (mean, 18% +/- 2%; n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC-containing colonies expressed the Langerhans cell/Birbeck granule specific marker molecule Lag. Without TGF-beta1 supplementation, Lag+ colony formation is minimal and formation of monocyte/macrophage-containing colonies predominates. Total cloning efficiency in the absence and presence of TGF-beta1 is virtually identical (mean, 41% +/- 6% v 41% +/- 4%). Thus, FL has the potential to strongly stimulate DC/LC generation, but has a strict requirement for TGF-beta1 to show this costimulatory effect.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, CD1 - metabolism
- Antigens, CD34 - metabolism
- Cell Aggregation -
- Culture Media, Serum-Free -
- Dendritic Cells - metabolism
- Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
- Hematopoiesis -
- Humans -
- Langerhans Cells - cytology Langerhans Cells - metabolism
- Membrane Proteins - metabolism
- Stem Cell Factor - metabolism
- Stem Cells - cytology Stem Cells - metabolism
- Transforming Growth Factor beta - metabolism
- Tumor Necrosis Factor-alpha - metabolism