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Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis
A D Wagner1, U Wittkop, A Prahst
1Medical School Hannover, Hannover, Germany.
Insights
Dendritic cells and T-cells co-localize in giant cell arteritis (GCA), suggesting dendritic cells present antigens. Bacterial presence, particularly Chlamydia pneumoniae, may trigger GCA via TNF alpha and TLR4 pathways.
Area of Science:
- Immunology
- Pathology
- Microbiology
Background:
- Giant cell arteritis (GCA) is an inflammatory vasculitis affecting large arteries.
- Co-localization of dendritic cells and Chlamydia pneumoniae observed in GCA vascular biopsies.
- The role of antigen-presenting cells and bacterial involvement in GCA pathogenesis requires further elucidation.
Purpose of the Study:
- To define the topographical relationship between dendritic cells and activated T-cells in GCA.
- To identify the antigen-presenting cell in GCA.
- To investigate biochemical and genetic factors, including bacterial roles, in GCA.
Main Methods:
- Analysis of 18 GCA temporal artery biopsies (PCR-positive for C. pneumoniae) using two-color immunohistochemistry.
- Investigation of GTP-binding proteins, TNF alpha, and TLR4.
- Comparison with 15 control temporal artery specimens.
Main Results:
- Dendritic cells were found in close proximity to activated CD4+ T cells within granulomatous infiltrates in GCA specimens.
- RhoA and Rac1 were present in granulomatous infiltrates.
- TNF alpha was expressed in dendritic cells, macrophages, and endothelial cells, particularly in granulomatous infiltrates and vasa vasorum; TLR4 was positive in dendritic cells, macrophages, and adventitial endothelial cells.
Conclusions:
- Immediate co-localization suggests dendritic cells act as antigen-presenting cells in GCA.
- RhoA and Rac1 may facilitate bacterial internalization and cell-cell contact.
- High TNF alpha and TLR4 expression in GCA tissues suggest their involvement in bacterial-induced inflammation.
Objective:
Giant cell arteritis (GCA) is a vasculitis predominantly affecting medium- and large-sized arteries. Recent data show the co-localization of dendritic cells and Chlamydia pneumoniae in vascular biopsies from GCA patients. Here we define the topographical relation of dendritic cells and these activated T-cells to determine the antigen presenting cell in GCA, and to examine several auxiliary biochemical and genetic aspects relating to the role of bacteria such as C. pneumoniae in eliciting GCA.
Methods:
18 paraffin-embedded temporal artery biopsy specimens from 14 patients with GCA that were PCR-positive for C. pneumoniae were examined by two-color immunohistochemistry for the topographical relationship between dendritic cells and activated T-cells. In addition the presence of GTP-binding proteins. Tumor necrosis factor alpha (TNF alpha), and Toll-like receptor 4 (TLR4) was investigated. 15 temporal artery specimens from 10 patients without GCA served as controls.
Results:
In all GCA specimens, dendritic cells co-localized in the immediate vicinity of activated CD4+ Talin-expressing T cells, and these were predominantly found in granulomatous infiltrates. Confocal microscopy confirmed the cell-cell contact of dendritic cells with activated T cells. Results further showed that RhoA and Rac1 were predominantly present in the region of granulomatous infiltrates. TNF alpha production and expression was found in dendritic cells and macrophages, predominantly in granulomatous infiltrates and in endothelial cells of the vasa vasorum dispersed in the adventitial and medial layers of the temporal artery. No control specimens showed TNF alpha expression. More than 95% of dendritic cells were positive for TLR4; macrophages and endothelial cells localized in the adventitia showed TLR4 production.
Conclusions:
The immediate co-localization of dendritic cells and activated T cells indicate a high probability that the former represent the antigen presenting cells in GCA. In addition, because of the presence of Rho A and Rac1 in the granulomatous infiltrates, we speculate that they provide the right environment for cell-cell contact and adhesion, and that they may promote the internalization of bacteria. TNF alpha is expressed at high levels in the granulomatous infiltrates of temporal artery specimens from patients with GCA. Since TLR4 is produced in the same cell types, and predominantly in the adventitial layer of the temporal artery, we suggest that these receptors are coupled to signal transduction pathways that control TNF alpha expression.