1. Dendritic cells generated with Flt3L and exposed to apoptotic cells lack induction of T cell anergy and Foxp3⁺ regulatory T cell conversion in vitro.
- Author
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Pletinckx K and Lutz MB
- Subjects
- Animals, Apoptosis, Cell Differentiation, Cells, Cultured, Clonal Anergy immunology, Forkhead Transcription Factors metabolism, Granulocyte-Macrophage Colony-Stimulating Factor immunology, Immunologic Memory, Lymphocyte Activation, Membrane Proteins immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phagocytosis, Thymocytes immunology, Thymocytes pathology, Bone Marrow Cells immunology, Dendritic Cells immunology, T-Lymphocyte Subsets immunology, T-Lymphocytes, Regulatory immunology
- Abstract
Removal of apoptotic cells, which appear during the steady state, is a pre-requisite to prevent generation of secondary necrotic cells that may lead to autoimmunity. The recognition of apoptotic material by dendritic cells (DCs) has been proposed to convert them into tolerogenic DCs equipped with specialized tolerogenic mechanisms on T cells. However, comparative studies to demonstrate functional alterations of DCs upon exposure to apoptotic cells have not been performed so far. Here we show that immature murine bone marrow-derived DCs generated with GM-CSF (GM-DCs) or Flt3L (FL-DCs) interact with live or apoptotic syngeneic thymocytes. As expected, GM-DCs phagocytose apoptotic but not live cells, FL-DCs only show trogocytosis of membrane parts. Interaction with live or apoptotic thymocytes did not lead to DC maturation. Both GM-DCs and FL-DCs present OVA as protein, peptide and membrane-associated antigens. Interestingly, only GM-DCs were able to induce T cell anergy or convert naïve T cells into FoxP3⁺ regulatory T cells (Tregs) but FL-DCs did not show either of these effects. Unexpectedly, exposure of immature GM-DCs to live or apoptotic thymocytes did not improve DC functions in both types of in vitro T cell tolerance induction assays. Together, our data suggest that these tolerogenic in vitro measures of immature BM-DCs are not further enhanced by exposure to apoptotic cells and may depend on the generating cytokine., (Copyright © 2013 Elsevier GmbH. All rights reserved.)
- Published
- 2014
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