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Vessel Wall–Embedded Dendritic Cells Induce T-Cell Autoreactivity and Initiate Vascular Inflammation
- Source :
- Circulation Research. 102:546-553
- Publication Year :
- 2008
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2008.
-
Abstract
- Human medium-sized and large arteries are targeted by inflammation with innate and adaptive immune responses occurring within the unique microspace of the vessel wall. How 3D spatial arrangements influence immune recognition and cellular response thresholds and which cell populations sense immunoactivating ligands and function as antigen-presenting cells are incompletely understood. To mimic the 3D context of human arteries, bioartificial arteries were engineered from collagen type I matrix, human vascular smooth muscle cells (VSMCs), and human endothelial cells and populated with cells implicated in antigen presentation and T-cell stimulation, including monocytes, macrophages, and myeloid dendritic cells (DCs). Responsiveness of wall-embedded antigen-presenting cells was probed with the Toll-like receptor ligand lipopolysaccharide, and inflammation was initiated by adding autologous CD4 + T cells. DCs colonized the outermost VSMC layer, recapitulating their positioning at the media–adventitia border of normal arteries. Wall-embedded DCs responded to the microbial product lipopolysaccharide by entering the maturation program and upregulating the costimulatory ligand CD86. Activated DCs effectively stimulated autologous CD4 T cells, which produced the proinflammatory cytokine interferon-γ and infiltrated deeply into the VSMC layer, causing matrix damage. Lipopolysaccharide-triggered macrophages were significantly less efficacious in recruiting T cells and promoting T-cell stimulation. CD14 + monocytes, even when preactivated, failed to support initial steps of vascular wall inflammation. Innate immune cells, including monocytes, macrophages, and DCs, display differential functions in the vessel wall. DCs are superior in sensing pathogen-derived motifs and are highly efficient in breaking T-cell tolerance, guiding T cells toward proinflammatory and tissue-invasive behavior.
- Subjects :
- Lipopolysaccharides
Physiology
T-Lymphocytes
CD14
medicine.medical_treatment
T cell
Antigen presentation
Cell Count
Biology
Models, Biological
Monocytes
Muscle, Smooth, Vascular
Immune system
medicine
Animals
Humans
Cells, Cultured
CD86
Antigen Presentation
Arteritis
Innate immune system
Tissue Engineering
Follicular dendritic cells
Macrophages
Cell Differentiation
Arteries
Dendritic Cells
Coculture Techniques
Rats
Cell biology
Toll-Like Receptor 4
Cytokine
medicine.anatomical_structure
Immunology
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....0529cb6d508e6a9d942b1bb474c5e648