Pituitary hormones modulate cell–cell interactions between thymocytes and thymic epithelial cells

Coelho, Valéria de Mello; Villa‐Verde, Déa Maria Serra; Dardenne, Mireille; Savino, Wilson

doi:10.1016/s0165-5728(97)00031-3

Cited by 77 publications

(76 citation statements)

References 37 publications

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“…Thus, the above experiments tell us that the transit of immature thymocytes through TNC is diminished in NOD mice, and that such a defect is related to the abnormally low VLA-5 expression. It is noteworthy that blocking experiments with anti-VLA-4 plus anti-VLA-5 mAb did not result in complete abrogation of thymocyte adhesion, which is in keeping with the role also played by laminin-mediated interactions in this event [37,38].…”

Section: Discussionsupporting

confidence: 69%

“…Thus, a functional deficiency of immature thymocytes correlates with the lower VLA-5 expression. As stated below, data related to all adhesion assays were presented as individual values due to variations in the adhesion degree, from experiment to experiment, as previously reported [37,38]. Yet, the results displayed in the panels are representative of at least three similar experiments.…”

Section: Vla-5 Defect In Nod Thymocytes Correlates With Decreased Immmentioning

confidence: 96%

“…Actually, some authors claim that TNC harbor CD4 -CD8 -and CD4 + CD8 + cells [35], whereas others sustain that typical TNC contain DP thymocytes [36]. In any case, since entrance and exit of thymocytes in TNC are dependent on ECM-mediated interactions, we considered TNC as an in vitro model for assessing thymocyte migration within the TEC context [34,[37][38]. We observed that TNC-derived epithelial cells from NOD mice produce ECM ligands, including fibronectin and laminin (not shown), and have no decrease in VLA-5 expression, compared to controls (Fig.…”

Section: Vla-5 Defect In Nod Thymocytes Correlates With Decreased Immmentioning

confidence: 99%

“…Thymocytes were pre-incubated with 1 mg/ml peptide solution for 30 min at 4˜C. Due to variations from experiment to experiment [38], data related to all adhesion assays were presented as individual values. The results displayed are representative of at least three similar experiments.…”

Section: Cell Adhesionmentioning

confidence: 99%

“…As explained above, in the case of adhesion assays, data were derived from individual experiments [34,38].…”

Section: Statistical Analysesmentioning

confidence: 99%

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Impaired migration of NOD mouse thymocytes: a fibronectin receptor‐related defect

et al. 2004

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We previously showed intrathymic alterations in non-obese diabetic (NOD) mice, including the appearance of giant perivascular spaces, filled with mature thymocytes, intermingled with an extracellular matrix network. This raised the hypothesis of a defect in thymocyte migration with partial arrest of exiting thymocytes in the perivascular spaces. Herein, we investigated the expression of receptors for fibronectin [very late antigen (VLA)-4 and VLA-5] and laminin (VLA-6), known to play a role in thymocyte migration. When compared with two normal and one other autoimmune mouse strains, a decrease of VLA-5 expression in NOD thymocytes was noticed, being firstly observed in late CD4/CD8 double-negative cells, and more pronounced in mature CD4 + and CD8 + thymocytes. Functionally, thymocyte exit from the lymphoepithelial complexes, the thymic nurse cells, was reduced. Moreover, NOD thymocyte adhesion to thymic epithelial cells as well as to fibronectin was diminished, and so was the migration of NOD thymocytes through fibronectin-containing transwell chambers. In situ, intra-perivascular space thymocytes were VLA-5-negative, suggesting a correlation between the thymocyte arrest within these structures and loss of VLA-5 expression. Overall, our data reveal impairment in NOD thymocyte migration, and correspond to the first demonstration of a functional fibronectin receptor defect in the immune system.

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Section: Discussionsupporting

confidence: 69%

Section: Vla-5 Defect In Nod Thymocytes Correlates With Decreased Immmentioning

confidence: 96%

Section: Vla-5 Defect In Nod Thymocytes Correlates With Decreased Immmentioning

confidence: 99%

Section: Cell Adhesionmentioning

confidence: 99%

“…As explained above, in the case of adhesion assays, data were derived from individual experiments [34,38].…”

Section: Statistical Analysesmentioning

confidence: 99%

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Impaired migration of NOD mouse thymocytes: a fibronectin receptor‐related defect

et al. 2004

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Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region

et al. 1999

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Epithelial cells are important components of the thymus microenvironment and are involved in thymocyte differentiation. The production and secretion of sulfated glycosaminoglycans by these cells grown in culture were investigated using labeling with radioactive 35S-Na2SO4 and 3H-glucosamine. The major glycosaminoglycans synthesized by these cells are heparan sulfate and hyaluronic acid. The structure of the heparan sulfate was investigated by the pattern of degradation products formed by deaminative cleavage with nitrous acid. The ratio 35S-sulfate/ H-glucosamine is high in the segments of the heparan sulfate released during the deaminative cleavage with nitrous acid but low in the resistant portion of the molecule. Thus, the heparan sulfate synthesized by the thymic epithelial cells contains a highly sulfated region. Digestion with heparitinase reveals that this highly sulfated region is a heparin-like segment of the molecule. The heparan sulfate is rapidly incorporated into the cell surface but its secretion to the extracellular medium requires a longer incubation period. Finally, heparin was used to mimic the possible effect of this heparan sulfate with a highly sulfated region, as ascertained by its ability to modulate thymocyte adhesion to thymic epithelial cells. Since heparin actually enhanced thymocyte adhesion, it is suggested that the heparan sulfate described herein, secreted by the thymic epithelium, may play a role upon intrathymic heterotypic cellular interactions.

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Is there a glycosaminoglycan-related heterogeneity of the thymic epithelium?

et al. 2000

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We determined the synthesis and secretion of glycosaminoglycans by three distinct preparations of mouse cultured thymic epithelial cells. These comprised primary cultures of thymic nurse cells (TNCs), which are normally located within the cortex of the thymic lobules, as well as two murine thymic epithelial cells, bearing a mixed, yet distinct, cortico-medullary phenotype. We first identified and measured the relative proportions of the various glycosaminoglycans in the three epithelial cells. Non-sulfated glycosaminoglycans are preponderantly secreted by the TNCs, while the sulfated glycans (particularly heparan sulfate) are relatively more abundant on the cell surface. The three types of epithelial cells differ markedly in their heparan sulfate composition, mainly due to different patterns of N- and O-sulfation. In addition, the cells differ in the synthesis and secretion of other glycosaminoglycans. Thus, TNCs secrete high amounts of dermatan sulfate + chondroitin sulfate to the culture medium. IT-76M1 cells secrete high proportions of heparan sulfate while 2BH4 cells show a more equilibrated proportion of dermatan sulfate/chondroitin sulfate and heparan sulfate. The three epithelial cells also differ in their capacity to produce hyaluronic acid and 2BH4 cells are distinguished by their high rate of synthesis of this glycosaminoglycan. In conclusion, our results show that distinct thymic epithelial cells can synthesize different types of glycosaminoglycans. Although it remains to be definitely determined whether these differences reflect the in vivo situation, our data provide new clues for further understanding of how glycosaminoglycan-mediated interactions behave in the thymus.

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Pituitary hormones modulate cell–cell interactions between thymocytes and thymic epithelial cells

Cited by 77 publications

References 37 publications

Impaired migration of NOD mouse thymocytes: a fibronectin receptor‐related defect

Impaired migration of NOD mouse thymocytes: a fibronectin receptor‐related defect

Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region

Is there a glycosaminoglycan-related heterogeneity of the thymic epithelium?

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