Distribution of lymphatic vessels in mouse thymus: immunofluorescence analysis

Odaka, Chikako; Morisada, Tohru; Oike, Yuichi; Suda, Toshio

doi:10.1007/s00441-005-0139-3

Cited by 25 publications

(27 citation statements)

References 38 publications

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“…It has been previously reported that CCL21 expression is associated with cortical capillaries (24). We confirmed this by examining fixed thymic tissue sections from mice injected with fluorescent lectin before sacrifice and stained with Abs for CCL21 (Fig.…”

Section: Dcs Localize Near Capillaries and Sources Of Ccl21 In The Thsupporting

confidence: 79%

“…Similar to the distribution of DCs reported herein, the chemokine CCL21, a ligand for CCR7, has also been reported to be concentrated in the medulla and present at lower levels throughout the thymic cortex (23,24). To explore the relative locations of DCs and CCL21 in the thymus, we stained fixed sections of adult thymic lobes from CD11cYFP reporter mice with Abs specific for the CCR7 ligand, CCL21 ( Fig.…”

Section: Dcs Localize Near Capillaries and Sources Of Ccl21 In The Thsupporting

confidence: 61%

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Thymocyte-Dendritic Cell Interactions near Sources of CCR7 Ligands in the Thymic Cortex

Ladi

Schwickert

Chtanova

et al. 2008

The Journal of Immunology

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Little is known about the dynamics of the interactions between thymocytes and other cell types, as well as the spatiotemporal distribution of thymocytes during positive selection in the microenvironment of the cortex. We used two-photon laser scanning microscopy of the mouse thymus to visualize thymocytes and dendritic cells (DCs) and to characterize their interactions in the cortex. We show that thymocytes make frequent contacts with DCs in the thymic cortex and that these associations increase when thymocytes express T cell receptors that mediate positive selection. We also show that cortical DCs and the chemokine CCL21 To what extent the cortex itself is divided into distinct functional compartments is not yet clear. At one end of the spectrum, it is possible that the cortex is functionally homogeneous. According to this view, cortical thymocytes would invariably be in contact with thymic epithelial cells capable of mediating positive selection, and positive selection could take place with equal probability throughout the cortex. On the other hand, there are indications that cortical thymic epithelial cells are heterogeneous (reviewed in Ref. 7), raising the possibility of functionally distinct regions of the cortex specialized for mediating selection events. The anatomical segregation of thymocytes in the cortex based on their TCR specificity provides an indication for such heterogeneity (8). However, distinct functional regions of the thymic cortex have not yet been identified. Two-photon laser scanning microscopy (TPLSM) provides an opportunity to examine the cellular migration and interaction events in tissues that underlie selection events within the thymus (reviewed in Ref. 9). Initial studies have revealed that thymocytes undergo a calcium-dependent stopping in response to positive selection signals in the thymus (10) and that interaction of thymocytes with MHC-bearing stromal cells can lead to prolonged but dynamic cell-cell contacts (11). Additionally, analysis of cell migration in the cortex of intact thymic lobes provided evidence that thymocytes move via a random walk in the cortex before positive selection and undergo rapid, directed migration to the medulla as a result of positive selection (12). These studies provide an early glimpse into the regulation of thymocyte migration by positive selection. However, the interactions of thymocytes with other cell types in the intact thymus and how these interactions change during the process of positive selection have not yet been addressed.Herein we examine the impact of the chemokine receptor CCR7 and TCR repertoire selection on thymocyte-DC interactions in the cortex of intact thymic lobes. We show that thymic DCs form intimate associations with cortical capillaries near sources of CCR7 ligands in the cortex. We find that thymocytes extensively

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Section: Dcs Localize Near Capillaries and Sources Of Ccl21 In The Thsupporting

confidence: 79%

Section: Dcs Localize Near Capillaries and Sources Of Ccl21 In The Thsupporting

confidence: 61%

Thymocyte-Dendritic Cell Interactions near Sources of CCR7 Ligands in the Thymic Cortex

Ladi

Schwickert

Chtanova

et al. 2008

The Journal of Immunology

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“…The previously known data on Prox1 function indicated the transcription factor plays an essential but potentially transient role as a binary switch during LEC differentiation in the embryo (Wigle and Oliver 1999;Wigle et al 2002). It was also clear that Prox1 expression in lymphatics persists into postnatal life, and a conspicuous down-regulation of Prox1 in the defective lymphatics of some mutant mouse models had been observed (Wilting et al 2002;Odaka et al 2006;Backhed et al 2007;Baluk and McDonald 2008). However, the relevance of these findings remained unclear.…”

Section: Lecs Are Reprogrammed In the Absence Of Prox1mentioning

confidence: 74%

Master and commander: continued expression of Prox1 prevents the dedifferentiation of lymphatic endothelial cells

Bixel¹,

Adams²

2008

Genes Dev.

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Cell differentiation occurs mostly during a specific developmental time window and is irreversible. The homeobox-containing transcription factor Prox1 is a master regulator of lymphatic endothelial cell differentiation in the embryo. A study by Johnson et al. (pp 3282-3291) published in this issueof Genes & Development now shows that continued expression of Prox1 is required to maintain lymphatic endothelial cell identity even in adult mice. These findings indicate that Prox1 is essential for the differentiation and function of the lymphatic vasculature throughout life.Endothelial cells (ECs) form two highly branched, treelike tubular networks in the vertebrate body, the blood vasculature and the lymphatic vasculature, which have distinct functional roles and morphological features. Blood vessels carry circulating blood through arteries into extensive capillary beds, the sites where gases, nutrients, and waste products are exchanged, and back into veins. In contrast, lymphatic vessels form a blind-ended system that drains protein-rich liquid, the lymph, through a network of distal capillaries (also known as terminal or initial lymphatics), larger collecting ducts and, finally, the thoracic duct into the venous system ( (Fig. 1). The specialization of blood vessels and lymphatic vessels and of the various subdomains within these endothelial networks are reflected by distinct gene expression profiles and signaling pathways (Fig. 2). For example, arterial ECs express a multitude of markers that are largely or entirely excluded from the venous or lymphatic endothelium (Lamont and Childs 2006;Adams and Alitalo 2007). The glycoprotein LYVE-1 is not only restricted to lymphatic ECs (LECs) but is also predominantly confined to the terminal capillaries within the lymphatic tree (Makinen et al. 2005;Baluk and McDonald 2008). Among the molecular markers that can be used to distinguish BECs and LECs, the homeobox-containing transcription factor Prox1 (prospero-related homeobox 1) is of particular importance. Prox1 is present in all nuclei throughout the lymphatic endothelium, and this pattern of expression is actually the earliest sign of lymphatic development when the first few LECs differentiate from BECs within a section of the cardinal vein (Wigle and Oliver 1999;Wigle et al. 2002). Prox1-master regulator of LEC differentiationLineage tracing experiments have demonstrated that lymphatic ECs in the mouse are derived from venous ECs during embryonic development (Srinivasan et al. 2007). A cluster of ECs in the cardinal vein start to express Prox1, leave the vessel and migrate into the adjacent tissue and form the first primitive lymphatic structures (

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“…The major components of the PVS are blood vessels to and from the medulla [2][3][4][5][6]. In addition large lymph vessels can be observed in the PVS often traveling down the septa and located adjacent to blood vessels [2,7]. They can be often observed to be packed with emigrating thymocytes [1,5].…”

Section: Introductionmentioning

confidence: 99%