Basic Science
Abstract # 2129: Vascular Dendritic Cells Sensing Microbial Motifs Instruct T Cells in Vascular Inflammation-a New Disease Model for Giant Cell Arteritis (GCA)
Authors: Wei Ma-Krupa, Augusto Vaglio, Stefan Gröschel, Olga Pryshchep, Kisha Piggott, Andrew T. Gewirtz, Jörg J. Goronzy, Cornelia M. Weyand. Emory University School of Medicine, Atlanta, GA
Objective: Having demonstrated that different vascular beds express unique TLR fingerprints, the authors wanted to: i) investigate whether resident DCs in the temporal artery vessel wall might be differentially regulated by TLR interactions, and ii) probe whether these stimulated DCs differentially activate unique groups of T cells in the local environment as a result.
Methods: Explanted temporal arteries (TAs) were evaluated by IHC for TLR expression, and functional studies were performed again using the implanted artery:SCID mouse model established by the authors. T cell activation and migration was assessed after the transfer of autologous mononuclear cells to the appropriate mouse, and examination of the artery implant.
Results: As shown in the first study, the TAs expressed a wide range of TLRs. When the chimeric mice were stimulated with TLR4 or TLR5, resident DCs in the adventitial layer of the implanted artery were stimulated. These stimulated DCs were able to recruit transferred autologous CD4+ T cells to the vessel wall. TLR4 DC-instructed T cells invaded deep into the artery wall, while TLR5 DC-instructed T cells were found more superficially.
Significance: Coupled with the accompanying abstract, this data provides further evidence for a potential pathogen-triggered initiating signal in GCA, perhaps mediated by ligation of specific TLRs. However, TLR4, which recognizes LPS (derived from gram negative bacteria), is relatively ubiquitous, and though was capable of instructing DCs to activate infiltrating CD4+ T cells, its activity in this regard would not explain the relative rarity of the development of GCA in the face of commonly occurring bascterial infections. Still, as novel concepts, these studies provide a true advance in our understanding of the potential pathogenesis of GCA and other arteritis syndromes.
