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The inflammatory activity of vascular lesions is driven by adaptive immune responses, with CD4 T cells undergoing clonal expansion in the vessel wall and releasing interferon \u03b3. Recent studies have described a distinctive population of dendritic cells (DCs) localized at the adventitia\u2010media border of normal medium\u2010sized arteries that appear to play a critical role in the initiation of vasculitis. Immune effector functions of this DC population are being examined in human artery\u2010severe combined immunodeficient (SCID) mouse chimeras. In their constitutive form, CD11c<jats:sup>+<\/jats:sup> fascin<jats:sup>+<\/jats:sup> adventitial DCs are not recognized by alloreactive T cells. Triggering with Toll\u2010like receptor (TLR) ligands is sufficient to break this state of tolerance and initiate DC activation, T\u2010cell recruitment, T\u2010cell activation, and T\u2010cell retention in the arterial wall. Systemic administration of ligands for TLR2 or \u20104 in human artery\u2010SCID chimeras drives differentiation of adventitial DCs into chemokine\u2010producing effector cells with high\u2010level expression of both CD83 and CD86 and mediates T\u2010cell regulatory function through release of interleukin 18. In established vasculitis, fully matured DCs retain antigen\u2010presenting function; antibody\u2010mediated DC depletion disrupts T\u2010cell and macrophage activation and has marked anti\u2010inflammatory effects. We conclude that adventitial DCs, an indigenous cell population of the arterial wall, are responsive to pathogen\u2010derived macromolecules and have gatekeeper function in regulating T\u2010cell recruitment and retention to the arterial adventitia. A switch of adventitial DCs from being nonstimulatory to T\u2010cell activating emerges as a critical event in the initiation of vasculitis.<\/jats:p>","DOI":"10.1196\/annals.1358.023","type":"journal-article","created":{"date-parts":[[2006,2,6]],"date-time":"2006-02-06T19:33:16Z","timestamp":1139254396000},"page":"195-208","source":"Crossref","is-referenced-by-count":83,"title":["Vascular Dendritic Cells in Giant Cell Arteritis"],"prefix":"10.1111","volume":"1062","author":[{"given":"CORNELIA M.","family":"WEYAND","sequence":"first","affiliation":[]},{"given":"WEI","family":"MA\u2010KRUPA","sequence":"additional","affiliation":[]},{"given":"OLGA","family":"PRYSHCHEP","sequence":"additional","affiliation":[]},{"given":"STEFAN","family":"GR\u00d6SCHEL","sequence":"additional","affiliation":[]},{"given":"ROBERTO","family":"BERNARDINO","sequence":"additional","affiliation":[]},{"given":"J\u00d6RG J.","family":"GORONZY","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2006,3,29]]},"reference":[{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.57.030195.004143"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/17402520400001652"},{"key":"e_1_2_12_4_2","first-page":"221","article-title":"Atherosclerosis: an inflammatory disease","volume":"26","author":"Liuzzo G.","year":"2001","journal-title":"Rays"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10016-004-0153-z"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.87.3.201"},{"issue":"8","key":"e_1_2_12_8_2","first-page":"S3","article-title":"Thoughts about the classification of small vessel vasculitis","volume":"17","author":"Falk R.J.","year":"2004","journal-title":"J. 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