α4 and α5 Integrins Costimulate the CD3-Dependent Proliferation of Fetal Thymocytes

Halvorson, Mark J.; Magner, William J.; Coligan, John E.

doi:10.1006/cimm.1998.1368

Cited by 5 publications

(4 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar levels of expression of CD44, LFA-1, and ␣ 4 and ␣ 5 integrins have been previously found on RTE and intrathymic cells (21). It has been previously demonstrated that SDF-1 up-regulates lymphocyte adhesion via ␣ 4 ␤ 7 integrin (22) and ␣ 4 and ␣ 5 integrins have been shown to play a role in the proliferation of fetal thymocytes (23,24). We studied the expression of these integrins in FTOC.…”

Section: Integrin Expression Does Not Account For Impaired Emigrationsupporting

confidence: 62%

A CXCR4-Dependent Chemorepellent Signal Contributes to the Emigration of Mature Single-Positive CD4 Cells from the Fetal Thymus

Vianello

Kraft

Mok

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both S1P-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62Lhigh and CD69low recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4 signaling was only partially overcome by the addition of the extrathymic chemoattractant S1P and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus.

show abstract

Section: Integrin Expression Does Not Account For Impaired Emigrationsupporting

confidence: 62%

A CXCR4-Dependent Chemorepellent Signal Contributes to the Emigration of Mature Single-Positive CD4 Cells from the Fetal Thymus

Vianello

Kraft

Mok

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…A previous study conducted in our laboratory has shown that the addition of antiintegrin mAbs rescues gastric adenocarcinoma cells from apoptosis despite suspended conditions [Caruso and McIntyre, 2001]. Other studies have shown that soluble collagen and fibronectin can also rescue cells from anoikis [Halvorson et al, 1998;Meerschaert et al, 1999]. In these cases mere ligation of integrins was enough to send the survival signal.…”

Section: Discussionmentioning

confidence: 96%

α4 integrin increases anoikis of human osteosarcoma cells

Marco

Díaz-Montero

Wygant

et al. 2003

J of Cellular Biochemistry

View full text Add to dashboard Cite

Cell motility, growth, and proliferation are regulated by adhesion to the extracellular matrix. Detachment of adherent cells from extracellular matrix results in induction of apoptosis ("anoikis"). Transformed cells often show an anchorage-independent growth that enables them to acquire a motile, invasive phenotype. This phenotype has been associated with the altered expression and function of the integrin family of transmembrane proteins that mediate cell adhesion to the extracellular matrix. Although alpha4 integrin is normally expressed on leukocyte subpopulations, a number of metastatic melanomas and sarcomas express it as well. In this study, we demonstrated the expression of alpha4 integrins on the human osteosarcoma cell line SAOS and on metastatic osteosarcoma lesions from the lung and pericardium. We further demonstrated that alpha4 integrin is coupled to the beta1 subunit by biochemical analysis and by using a mAb directed against a combinatorial epitope unique to the alpha4beta1 molecule. SAOS cells undergo anoikis when adherence is denied. Anoikis involved the activation of caspase 3 and the release of cytochrome c from mitochondria. Treatment of non-adherent SAOS with an anti-alpha4 mAb increased anoikis while anti-beta1 integrin mAbs did not alter anoikis, thus indicating a novel function for the alpha4 subunit in the control of cell death. Since integrins can control cell migration, proliferation, and apoptosis these results demonstrate a potential role for alpha4 integrin during multiple aspects of osteosarcoma metastasis.

show abstract

“…Fibronectin and laminins as prominent representatives of extracellular matrix molecules have been shown to either enhance or downregulate cell proliferation of developing T cells (Halvorson et al, 1998;Vivinus-Nebot et al, 1999). Cellular adhesion of human CD103 + CD8 + SP thymocytes to epithelial carcinoma cells did not lead to enhanced thymocyte proliferation, whereas adhesive interactions of these thymocytes with cultivated thymic epithelial cells did.…”

Section: Discussionmentioning

confidence: 99%

E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation

Kutlesa

Wessels

Speiser

et al. 2002

Journal of Cell Science

View full text Add to dashboard Cite

Cadherins are a family of cell adhesion molecules that mainly mediate homotypic homophilic interactions, but for E-cadherin, heterophilic interactions with the integrin αE(CD103)β7have also been reported. In the human thymus, where thymocytes develop in close contact with thymic stromal cells, E-cadherin expression was detected on thymic epithelial cells. By immunofluorescence staining, the strongest expression of E-cadherin was observed on medullary thymic epithelial cells. These cells also express cytosolic catenins, which are necessary to form functional cadherin-catenin complexes. Regardless of their developmental stage, human thymocytes do not express E-cadherin, indicating that homophilic interactions cannot occur. Flow cytometric analysis revealed that the E-cadherin ligand CD103 is expressed on subpopulations of the early CD4- CD8- double-negative and of the more mature CD8+ single-positive thymocytes. Using an in vitro cell adhesion assay, double-negative and CD8+ single-positive thymocytes adhered strongly to isolated thymic epithelial cells. These adhesive interactions could be inhibited by antibodies against E-cadherin or CD103. CD8+thymocytes showed a proliferative response when incubated with thymic epithelial cells. This mitogenic effect was inhibited by antibodies against CD103, which strongly indicates a direct involvement of the adhesive ligand pair CD103—E-cadherin in human thymocyte cell proliferation.

show abstract

α4 and α5 Integrins Costimulate the CD3-Dependent Proliferation of Fetal Thymocytes

Cited by 5 publications

References 46 publications

A CXCR4-Dependent Chemorepellent Signal Contributes to the Emigration of Mature Single-Positive CD4 Cells from the Fetal Thymus

A CXCR4-Dependent Chemorepellent Signal Contributes to the Emigration of Mature Single-Positive CD4 Cells from the Fetal Thymus

α4 integrin increases anoikis of human osteosarcoma cells

E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation

Contact Info

Product

Resources

About