The conveyor belt hypothesis for thymocyte migration: participation of adhesion and de-adhesion molecules

Villa‐Verde, Déa Maria Serra; Calado, Tereza C. S.; Ocampo, J.S.P.; Silva, Elisangela; Savino, Wilson

doi:10.1590/s0100-879x1999000500010

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…In this regard, we recently proposed that the substrate for such migration corresponds to microenvironmental cell‐derived ECM components, organized in a supramolecular arrangement, within the thymic lobules 40. In theory, sequential adhesion and de‐adhesion of migrating thymocytes would take place in this process 41. We postulate that galectin‐3 would favor the de‐adhesion step.…”

Section: Discussionmentioning

confidence: 98%

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment

et al. 2002

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The process of thymocyte differentiation occurs within the context of the thymic microenvironment, in which T cell precursors interact with thymic microenvironmental cells and extracellular matrix. Here we studied the expression of galectin‐3, a β‐galactoside binding lectin, in the thymus of young adult mice. Galectin‐3 was found mainly in the medulla and to a lesser extent in the cortex. We further showed that distinct microenvironmental elements, such as thymic epithelial cells, the epithelial component of thymic nurse complexes and phagocytic cells of the thymic reticulum produce, secrete and accumulate galectin‐3 on the cell surface. Functionally, galectin‐3‐enriched medium inhibited in vitro thymocyte interactions with thymic microenvironmental cells, accelerated the release of thymocytes from thymic nurse cells and inhibited the reconstitution of these lymphoepithelial complexes. These effects were blocked by exogenous lactose (Galβ1–4Glc), but not melibiose (Galα1–6Glc), and by a monospecific anti‐galectin‐3 antibody. Recombinant galectin‐3 also inhibited thymocyte/thymic epithelial cell interactions. Our data indicate that intrathymically produced galectin‐3 disrupts thymocyte/microenvironmental cell interactions, thus acting as a de‐adhesion molecule.

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Section: Discussionmentioning

confidence: 98%

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment

et al. 2002

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“…Cell migration is a complex process that sequentially involves adhesion and deadhesion events [5], combined with cellular strategies that surmount the biophysical resistance imposed by three-dimensional microenvironments [6,7]. The formation of adhesion sites stabilizes the newly formed cellular extensions and permits the cell to exert forces against the substrate [8].…”

Section: Introductionmentioning

confidence: 99%

Triiodothyronine Modulates Extracellular Matrix-Mediated Interactions between Thymocytes and Thymic Microenvironmental Cells

Ribeiro-Carvalho

Farias-de-Oliveira²,

Villa‐Verde³

et al. 2002

Neuroimmunomodulation

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Objectives: Thyroid hormones exert immunomodulatory activities and the thymus is one of their target organs. We previously showed that triiodothyronine (T₃) modulates thymic hormone production and extracellular matrix (ECM) expression by mouse thymic epithelial cells (TEC). This concept is enlarged herein by studying the effects of T₃ in human TEC preparations including primary cultures derived from thymic nurse cell complexes, as well as human and murine TEC lines. Methods and Results: We observed that in all cases, ECM ligands and receptors (such as fibronectin, laminin, VLA-5 and VLA-6) are enhanced in vitro, as ascertained by immunocytochemistry, ELISA and cytofluorometry. Moreover, thymocyte adhesion to these TEC preparations is augmented by T₃. Interestingly, TEC-thymocyte adhesion is also upregulated when thymocytes from T₃-treated mice adhere to untreated TEC cultures. Such an enhancing effect of T₃ upon TEC-thymocyte interactions is likely due to the increase in the expression of ECM ligands and receptors, since it is prevented when T₃-treated TEC cultures are incubated with anti-ECM antibodies prior to the adhesion assay. We then tested whether T₃ could modulate interactions between thymocytes and nonepithelial microenvironmental cells, exemplified herein by the phagocytic cells of the mouse thymic reticulum. In fact, in vitro treatment of these cells with T₃ increases ECM ligands and receptors and augments their ability to adhere to thymocytes. Lastly, using immunochemistry-based assays, we showed the presence of the nuclear T₃ receptor in all thymic microenvironmental cell preparations. Conclusion: Our data show that T₃ upregulates ECM-mediated heterocellular interactions of thymocytes with distinct thymic microenvironmental cells, in both humans and mice.

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“…Integrins are receptors for these extracellular matrix components. The b 1 a 5 integrin is one of the fibronectin receptors, and the b 1 a 6 intergrin, for example, has been described as a ligand for laminin 2, which is also known as merosin (Villa-Verde et al 1999;Iwao et al 2000;Yanagawa et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro

2003

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2,3,7,8-Tetrachloro-dibenzo- p-dioxin (TCDD) is a ubiquitously distributed xenobiotic. The adverse effects of TCDD on the mammalian immune system have been studied for decades, but it is still unclear whether TCDD has direct effects on T-lymphocytes or whether it acts via the thymic microenvironment. We have studied the effects of TCDD on primary cultures of human thymic epithelial cells (TEC) focusing on differentiation markers, integrins and adhesion molecules involved in cell-cell and in cell-matrix interactions. TEC were treated with TCDD at concentrations of 0.001, 0.01, 0.1, 1.0 or 10.0 nM or with 100 nM PCB 126 (3,3',4,4',5-pentachlorobiphenyl) for 3 days, and were then analysed by flow cytometry for expression of surface antigens using monoclonal antibodies against Hassall's bodies (TE-8, TE-16) or against surface structures such as CD29, CD49b, CD49e, CD49f, CD51, CD54, CD58, CD61 and CD106. At TCDD concentrations as low as 0.01 nM we found a significant increase in terminally differentiated, TE-16-positive TEC; at a ten-fold greater concentration the number of cells marked with the TE-8 antibody was also increased. With both markers the most pronounced effect (approximately +15%) was observed at 1 nM TCDD. An increase of cells expressing the integrin alpha-chains CD49b, CD49e and CD51 as well as CD54 was observed at concentrations of 0.1 nM TCDD or higher. The proportion of cells expressing CD106 or CD49f decreased significantly upon treatment with TCDD. No effects on the integrin beta-chains CD29 and CD61 could be detected. Overall, PCB 126 induced similar changes to TCDD. In summary, TCDD and a coplanar PCB induced terminal differentiation of human TEC along with changes of integrins and other adhesion molecules. These receptors and their interplay with the extracellular matrix have key functions in the maturation of T-lymphocytes and it is plausible that their alteration would be involved in TCDD-induced immunotoxicity.

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The conveyor belt hypothesis for thymocyte migration: participation of adhesion and de-adhesion molecules

Cited by 9 publications

References 23 publications

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment

Triiodothyronine Modulates Extracellular Matrix-Mediated Interactions between Thymocytes and Thymic Microenvironmental Cells

Effects of 2,3,7,8-TCDD and PCB 126 on human thymic epithelial cells in vitro

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