Vascular Dendritic Cells in Giant Cell Arteritis WEYAND, CORNELIA M.; MA-KRUPA, WEI; PRYSHCHEP, OLGA ...
Annals of the New York Academy of Sciences,
December 2005, Volume:
1062, Issue:
1
Journal Article
Peer reviewed
: Giant cell arteritis (GCA) is a granulomatous vasculitis that selectively targets medium‐sized and large arteries, especially the cranial branches of the aorta. 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 γ. Recent studies have described a distinctive population of dendritic cells (DCs) localized at the adventitia‐media border of normal medium‐sized 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‐severe combined immunodeficient (SCID) mouse chimeras. In their constitutive form, CD11c+ fascin+ adventitial DCs are not recognized by alloreactive T cells. Triggering with Toll‐like receptor (TLR) ligands is sufficient to break this state of tolerance and initiate DC activation, T‐cell recruitment, T‐cell activation, and T‐cell retention in the arterial wall. Systemic administration of ligands for TLR2 or ‐4 in human artery‐SCID chimeras drives differentiation of adventitial DCs into chemokine‐producing effector cells with high‐level expression of both CD83 and CD86 and mediates T‐cell regulatory function through release of interleukin 18. In established vasculitis, fully matured DCs retain antigen‐presenting function; antibody‐mediated DC depletion disrupts T‐cell and macrophage activation and has marked anti‐inflammatory effects. We conclude that adventitial DCs, an indigenous cell population of the arterial wall, are responsive to pathogen‐derived macromolecules and have gatekeeper function in regulating T‐cell recruitment and retention to the arterial adventitia. A switch of adventitial DCs from being nonstimulatory to T‐cell activating emerges as a critical event in the initiation of vasculitis.
Inflammatory vasculopathies, ranging from the vasculitides (Takayasu arteritis, giant cell arteritis, and polyarteritis nodosa) to atherosclerosis, display remarkable target tissue tropisms for ...selected vascular beds. Molecular mechanisms directing wall inflammation to restricted anatomic sites within the vascular tree are not understood. We have examined the ability of 6 different human macrovessels (aorta and subclavian, carotid, mesenteric, iliac, and temporal arteries) to initiate innate and adaptive immune responses by comparing pathogen-sensing and T-cell-stimulatory capacities.
Gene expression analysis for pathogen-sensing Toll-like receptors (TLRs) 1 to 9 showed vessel-specific profiles, with TLR2 and TLR4 ubiquitously present, TLR7 and TLR9 infrequent, and TLR1, TLR3, TLR5, TLR6, and TLR8 expressed in selective patterns. Experiments with vessel walls stripped of the intimal or adventitial layer identified dendritic cells at the media-adventitia junction as the dominant pathogen sensors. In human artery-severe combined immunodeficiency (SCID) mouse chimeras, adoptively transferred human T cells initiated vessel wall inflammation if wall-embedded dendritic cells were conditioned with TLR ligands. Wall-infiltrating T cells displayed vessel-specific activation profiles with differential production of CD40L, lymphotoxin-alpha, and interferon-gamma. Vascular bed-specific TLR fingerprints were functionally relevant, as exemplified by differential responsiveness of iliac and subclavian vessels to TLR5 but not TLR4 ligands.
Populated by indigenous dendritic cells, medium and large human arteries have immune-sensing and T-cell-stimulatory functions. Each vessel in the macrovascular tree exhibits a distinct TLR profile and supports selective T-cell responses, imposing vessel-specific risk for inflammatory vasculopathies.
Plotless density estimators are those that are based on distance measures rather than counts per unit area (quadrats or plots) to estimate the density of some usually stationary event, e.g. burrow ...openings, damage to plant stems, etc. These estimators typically use distance measures between events and from random points to events to derive an estimate of density. The error and bias of these estimators for the various spatial patterns found in nature have been examined using simulated populations only. In this study we investigated eight plotless density estimators to determine which were robust across a wide range of data sets from fully mapped field sites. They covered a wide range of situations including animal damage to rice and corn, nest locations, active rodent burrows and distribution of plants. Monte Carlo simulations were applied to sample the data sets, and in all cases the error of the estimate (measured as relative root mean square error) was reduced with increasing sample size. The method of calculation and ease of use in the field were also used to judge the usefulness of the estimator. Estimators were evaluated in their original published forms, although the variable area transect (VAT) and ordered distance methods have been the subjects of optimization studies.
An estimator that was a compound of three basic distance estimators was found to be robust across all spatial patterns for sample sizes of 25 or greater. The same field methodology can be used either with the basic distance formula or the formula used with the Kendall-Moran estimator in which case a reduction in error may be gained for sample sizes less than 25, however, there is no improvement for larger sample sizes. The variable area transect (VAT) method performed moderately well, is easy to use in the field, and its calculations easy to undertake.
Plotless density estimators can provide an estimate of density in situations where it would not be practical to layout a plot or quadrat and can in many cases reduce the workload in the field.
In modern business entities intellectual capital is very important. It usually determines the innovation of solutions and ensures proper relations with the customers. Market efficiency of staff is ...supported by sophisticated tools and instruments. One of them is the business model strategy for RTE. An important role is also played by coaching techniques.
As a result of the new economic policy, fourteen Economic and Technological Development Zones (ETDZs) were established in twelve coastal cities between 1984 and 1988. The first ETDZs were Dalian, ...Yantai, Qingdao, Lianyungang, Nantong, Minhang (Shanghai), Hongqiao (Shanghai), Caohejing (Shanghai), Ningbo, Fuzhou, Guangzhou and Zhanjiang. Unlike Special Economic Zone (SEZ), an ETDZ is located in the suburban area of a major city. Special policies are adopted within the ETDZ. An administrative committee, normally selected by the local government, oversees economic and social management in the zones on behalf of the local government. The category ‘SEZ’ covers a broad range of more specific zone types, including Free Trade Zones (FTZ), Export Processing Zones (EPZ), Free Zones (FZ), Industrial Estates (IE), Free Ports, Urban Enterprise Zones and others. The second wave of expansion of ETDZs was led by the establishment of Pudong New District in Shanghai in 1990. This decision was aimed at elevating the status of Shanghai, making it the “Dragon Head” of the Yangtze River Delta Region, which comprises of Shanghai and parts of Jiangsu and Zhejiang. Prior to the establishment of this new district, the Pearl River Delta Region – comprising nine cities in Guangdong – was the forerunner of China’s open door policy. However, unlike Guangdong, which lies at the south-eastern coast of China, Shanghai’s economic development will have more impact on China’s vast hinterland. Between 1992 and 1993, a total of eighteen state-level ETDZs were established – Yingkou, Changchun, Shenyang, Harbin, Weihai, Kunshan, Hangzhou, Xiaoshan, Wenzhou, Rongqiao, Dongshan, Guangzhou Nansha, Huizhou Daya Bay, Wuhu, Wuhan, Chongqing, Beijing and Urumchi. Two special projects were added later. Founded in 1993, the Ningbo Daxie Development Zone is an investment by China International Trust and Investment Corporation (CITIC), and comes under its management. The other special project is the Suzhou Industrial Park, which was founded in 1994, and is a joint cooperation between the governments of China and Singapore. After 2000, in an effort to fuel the development of the Central and Western regions, the central government also endorsed the establishment of a further eleven national ETDZs in inland regions. Up till now, China has a total of fifty-four state-level ETDZs – thirty-two in coastal regions, and twenty-two in the hinterland. The region of Hong Kong has a role and status of innovation. The planners in this unique part of East Asia expect that some new concepts can help the former British colony to embrace a new economic model: a model in which design, marketing and branding play the crucial role in economy.
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