Stromal Cell Networks Regulate Lymphocyte Entry, Migration, and Territoriality in Lymph Nodes

Bajénoff, Marc; Egen, Jackson G.; Koo, Lily Y.; Laugier, J; Brau, Frédéric; Glaichenhaus, Nicolas; Germain, Ronald N.

doi:10.1016/j.immuni.2006.10.011

Cited by 834 publications

(953 citation statements)

References 54 publications

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“…The instantaneous and mean velocities of T cells, their mean free paths, and their trajectories in the presence and the absence of Ag-presenting dendritic cells can thus be determined. Further, such experiments have revealed that T cells move by crawling along the strands of a fibroblastic reticular cell (FRC) 4 network (1). Remarkably, trajectories of individual T cells obtained from these studies suggest that T cell motion is random and not directed by chemokine gradients over large distances.…”

Section: Ovement Of T Cells Within Lymphoid Organs Facilitatesmentioning

confidence: 95%

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Characterizing T Cell Movement within Lymph Nodes in the Absence of Antigen

Beauchemin

Dixit

Perelson

2007

The Journal of Immunology

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The recent application of two-photon microscopy to the visualization of T cell movement has presented trajectories of individual T cells within lymphoid organs both in the presence and in the absence of Ag-loaded dendritic cells. Remarkably, even though T cells largely move along conduits of the fibroblastic reticular cell network, they appear to execute random walks in lymphoid organs rather than chemotaxis. In this study, we analyze experimental trajectories of T cells using computer simulations of idealized random walks. Comparisons of simulations with experimental data provide estimates of key parameters that characterize T cell motion in vivo. For example, we find that the distance moved before turning is about twice the distance between intersections in the fibroblastic reticular cell network, suggesting that at an intersection a T cell will turn onto a new fiber ∼50% of the time. Although the calibrated model appears to offer an accurate representation of T cell movement, it has also uncovered inconsistencies across different experimental data sets.

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Section: Ovement Of T Cells Within Lymphoid Organs Facilitatesmentioning

confidence: 95%

“…Two-photon microscopy has allowed the direct visualization of the movement of T cells within lymph nodes, giving new insights into immune interactions (1)(2)(3)(4). From these experiments, the locations of individual T cells moving in lymphoid organs are obtained as a function of time (5)(6)(7)(8).…”

Section: Ovement Of T Cells Within Lymphoid Organs Facilitatesmentioning

confidence: 99%

Characterizing T Cell Movement within Lymph Nodes in the Absence of Antigen

Beauchemin

Dixit

Perelson

2007

The Journal of Immunology

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“…The extracellular matrix inside the FRC network has been termed conduit [6] due to its function as transporting system for small soluble antigens from the afferent lymph directly to the HEV, without percolating through the lymphocyte compartment [3]. Besides its critical function in directing the transport of soluble antigens, the FRC network orchestrates the directed movement of dendritic cells (DC), T and B cells within the lymph node to enhance the frequency of their encounters [4,7].…”

Section: Introductionmentioning

confidence: 99%

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

et al. 2008

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Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1 + sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.

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“…More recently it has been shown that the vast majority of lymph node T cells actively follow along fibers of the fibroblastic reticular cell network. Presumably the choice of which branch to follow is random unless an inflammatory response alters the presence of or sensitivity to factors that would favor one path over another [31,32]. The absence of this specialized matrix in the iris stroma likely contributes to the slower speed that we observed for T cells migrating in the iris.…”

Section: Discussionmentioning

confidence: 90%

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

Rosenbaum

Ronick

Song

et al. 2008

Clinical Immunology

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Videomicroscopy is being used increasingly to characterize the interaction of T cells and antigenpresenting cells (APCs) within lymphatic tissues but has not been reported, to our knowledge, at sites of inflammation. We employed intravital videomicroscopy to study an anterior uveitis model using DO11.10 T cells and ovalbumin (OVA). T cell movement in iris was consistent with a random walk independent of the presence of recognized antigen and had a lateral speed slower than T cells in lymph node. Lingering of T cells adjacent to APCs suggested that they were physically interacting. This apparent contact demonstrated antigen specificity when comparing results from DO11.10 cells with OVA versus bovine serum albumin (BSA) loaded APCs but not when comparing results from OVA-loaded APCs with DO11.10 versus HA clonotype 6.5 T cells. Further studies with this model system should clarify the contribution of T cell-APC communication at a site of inflammation, infection, or immunization.

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Stromal Cell Networks Regulate Lymphocyte Entry, Migration, and Territoriality in Lymph Nodes

Cited by 834 publications

References 54 publications

Characterizing T Cell Movement within Lymph Nodes in the Absence of Antigen

Characterizing T Cell Movement within Lymph Nodes in the Absence of Antigen

Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node

T cell–antigen-presenting cell interactions visualized in vivo in a model of antigen-specific inflammation

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