Bone Marrow Precursors of Nonobese Diabetic Mice Develop into Defective Macrophage-Like Dendritic Cells In Vitro
Autor: | Pieter J. M. Leenen, Hemmo A. Drexhage, Marjolijn Bunk, Tatjana Nikolic |
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Rok vydání: | 2004 |
Předmět: |
Myeloid
Acid Phosphatase Immunology CD11c Apoptosis Bone Marrow Cells Nod Biology Leukocyte Count Mice Mice Inbred NOD medicine Animals Immunology and Allergy Macrophage Cells Cultured Myeloid Progenitor Cells NOD mice Mice Inbred BALB C Mice Inbred C3H Macrophages Monocyte Granulocyte-Macrophage Colony-Stimulating Factor Membrane Proteins Cell Differentiation Dendritic Cells Leukopenia In vitro Cell biology Mice Inbred C57BL medicine.anatomical_structure Female Bone marrow Lysosomes Biomarkers Cell Division |
Zdroj: | The Journal of Immunology. 173:4342-4351 |
ISSN: | 1550-6606 0022-1767 |
Popis: | The NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid precursors into non-DC in response to GM-CSF was not considered. In this study, we demonstrate several abnormalities during myeloid differentiation of NOD BM precursors using GM-CSF in vitro. 1) We found reduced proliferation and increased cell death in NOD cultures, which explain the previously reported low yield of DC progeny in NOD. Cell yield in NOR cultures was normal. 2) In a detailed analysis GM-CSF-stimulated cultures, we observed in both NOD and NOR mice an increased frequency of macrophages, identified as CD11c+/MHCII− cells with typical macrophage morphology, phenotype, and acid phosphatase activity. This points to a preferential maturation of BM precursors into macrophages in mice with the NOD background. 3) The few CD11c+/MHCIIhigh cells that we obtained from NOD and NOR cultures, which resembled prototypic mature DC, appeared to be defective in stimulating allogeneic T cells. These DC had also strong acid phosphatase activity and elevated expression of monocyte/macrophage markers. In conclusion, in this study we describe a deviated development of myeloid BM precursors of NOD and NOR mice into macrophages and macrophage-like DC in vitro. Potentially, these anomalies contribute to the dysfunctional regulation of tolerance in NOD mice yet are insufficient to induce autoimmune diabetes because they occurred partly in NOR mice. |
Databáze: | OpenAIRE |
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