Extracellular matrix proteins in intrathymic T-cell migration and differentiation?

Savino, Wilson; Villa‐Verde, Déa Maria Serra; Lannes‐Vieira, Joseli

doi:10.1016/0167-5699(93)90278-s

Cited by 94 publications

(52 citation statements)

References 27 publications

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“…Since intrathymic T cell development occurs concomitantly to migratory activity [23,24], we and others studied intrathymic interactions involving ECM ligands and receptors [25,26]. The fibronectin receptors very late antigen (VLA)-4 and VLA-5 are relevant in intrathymic T cell development [27][28][29][30], and likely participate in the control of apoptosis [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

et al. 2004

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“…During their intrathymic journey, thymocytes rely on adhesion molecules and receptors for extracellular matrix proteins as important driving force (LannesVieira et al 1991;Savino et al 1993). It is reasonable to assume that some of these molecules might also play a role in TNC and ROS formation in vivo.…”

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confidence: 99%

Murine Thymic Nurse Cells and Rosettes: Analysis of Adhesion Molecule Expression Using Confocal Microscopy and a Simplified Enrichment Method

Oliveira-dos-Santos

Rieker–Geley

Recheis

et al. 1997

J Histochem Cytochem.

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SUMMARY Thymic nurse cells (TNC) and T-cell stromal rosettes (ROS) are two in vivo models for stromal cell-thymocyte interactions. We describe a simplified enrichment method for TNC and ROS that overcomes the necessity for large amounts of tissue. The complexes were further analyzed with confocal microscopy, and three subunits of ROS were defined on the basis of their central cell phenotype, i.e., macrophage, dendritic, or epithelial cell rosettes. Because adhesion molecules are proposed to play a crucial role in T-cell development, we investigated CD44, LFA-1, and ICAM-1 expression in such complexes. The epithelial component of TNC expresses CD44 and ICAM-1, whereas intra-TNC thymocytes are LFA-negative. With regard to ROS, all subsets expressed CD44, and macrophage and dendritic cell ROS were also ICAM-1-positive and LFA-1-positive. The current protocol opens the possibility for further in vivo analysis of stromal cell-thymocyte interactions, e.g., for studies of scarce gene mutant mice.

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“…We previously demonstrated that thymocyte adhesion to cultured thymic epithelial cells (TEC) is enhanced in the presence of ECM proteins, such as fibronectin and laminin, and diminished in the presence of corresponding anti-ECM and ECM receptor antibodies [17,18]. Additionally, chemokines, a group of soluble peptides, play a combined role with ECM on thymocyte migration [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Triiodothyronine Modulates Thymocyte Migration

Ribeiro-Carvalho

Lima-Quaresma

Mouço³

et al. 2007

Scand J Immunol

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Triiodothyronine (T3) exerts several effects on thymus physiology. In this sense, T3 is known to stimulate thymic microenvironmental cells to enhance the production of extracellular matrix (ECM) moieties, which are relevant in thymocyte migration. Here, we further investigated the in vivo influence of T3 on ECM production, as well as on ECM‐related T‐cell migration events. For this, BALB/c mice were subjected to two protocols of T3 treatment: long‐term (30 days) i.p. daily T3 injections or short‐term (16 h) after a single T3 intrathymic injection. These two treatments did promote an enhancement in the expression of fibronectin and laminin, in both cortex and medullary regions of the thymic lobules. As revealed by the long‐term treatment, the expression of ECM protein receptors, including VLA‐4, VLA‐5 and VLA‐6, was also increased in thymocyte subsets issued from T3‐treated mice. We further used thymic nurse cells (TNC) as an in vitro system to study the ECM‐related migration of immature thymocytes in the context of thymic epithelial cells. Even a single intrathymic injection of T3 resulted in an increase in the ex vivo exit of thymocytes from TNC lymphoepithelial complexes. Accordingly, when we evaluated thymocyte migration in transwell chambers pre‐coated with ECM proteins, we found an increase in the numbers of migrating cells, when thymocytes were derived from T3‐treated mice. Overall, our data show that in vivo intrathymic short‐term i.p. long‐term T3 treatments are able to modulate thymocyte migration, probably via ECM‐mediated interactions.

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Extracellular matrix proteins in intrathymic T-cell migration and differentiation?

Cited by 94 publications

References 27 publications

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

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

Murine Thymic Nurse Cells and Rosettes: Analysis of Adhesion Molecule Expression Using Confocal Microscopy and a Simplified Enrichment Method

Triiodothyronine Modulates Thymocyte Migration

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