CXCL12-driven thymocyte migration is increased by thymic epithelial cells treated with prolactin in vitro

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium.

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

Archives of Toxicology ◽

10.1007/s00204-003-0445-z ◽

2003 ◽

Vol 77 (6) ◽

pp. 358-364 ◽

Cited By ~ 9

Author(s):

Kai Riecke ◽

André Schmidt ◽

Ralf Stahlmann

Keyword(s):

Epithelial Cells ◽

Thymic Epithelial Cells ◽

Pcb 126

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Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.83.17.6588 ◽

1986 ◽

Vol 83 (17) ◽

pp. 6588-6592 ◽

Cited By ~ 37

Author(s):

K. H. Singer ◽

L. S. Wolf ◽

D. F. Lobach ◽

S. M. Denning ◽

D. T. Tuck ◽

...

Keyword(s):

Epithelial Cells ◽

Thymic Epithelial Cells

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In vitro growth and maintenance of two morphologically distinct populations of thymic epithelial cells

Cellular Immunology ◽

10.1016/0008-8749(85)90208-4 ◽

1985 ◽

Vol 90 (2) ◽

pp. 439-450 ◽

Cited By ~ 23

Author(s):

A.C. Nieburgs ◽

P.T. Picciano ◽

J.H. Korn ◽

T. McCalister ◽

C. Allred ◽

...

Keyword(s):

Epithelial Cells ◽

Thymic Epithelial Cells ◽

In Vitro Growth

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Upregulated Expression of Fibronectin Receptors Underlines the Adhesive Capability of Thymocytes to Thymic Epithelial Cells During the Early Stages of Differentiation: Lessons From Sublethally Irradiated Mice

Blood ◽

10.1182/blood.v93.3.974.403k19_974_990 ◽

1999 ◽

Vol 93 (3) ◽

pp. 974-990

Author(s):

Sergio R. Dalmau ◽

Claudia S. Freitas ◽

Wilson Savino

Keyword(s):

Epithelial Cells ◽

Cell Attachment ◽

Whole Body ◽

Thymic Epithelial Cells ◽

Strongly Correlated ◽

Enhanced Expression ◽

Single Positive ◽

Young Stage ◽

And Function

A 250-cGy whole-body γ-radiation dose was used to induce thymus regression in mice, and to study the expression and function of extracellular matrix (ECM) receptors in distinct thymocyte subsets emerging during repopulation of the organ. The onset of regeneration was detected from day 2 to 3 postirradiation (P-Ir), when a remarkable increase in the absolute counts of CD3−CD25hiCD44+ and CD3−CD25in/hiCD44−cells occurred. Enhanced expression of L-selectin, 4, and 5 integrin chains (L-selhi 4hi5hi) was also exhibited by these cells. This pattern of expression was maintained until the CD4+CD8+ (DP) young stage was achieved. Afterward, there was a general downregulation of these ECM receptors in DP as well as in CD4+ or CD8+ single positive (SP) thymocytes (L-selin 4in5in). In some recently generated SP cells, 4 expression was downregulated before the 5 chain, and L-selectin was upregulated in half of more mature cells. The expression of the 6 integrin chain was downregulated only in maturing CD4+cells. Importantly, the increased expression of L-selectin and 4 and 5 chains in thymocytes was strongly correlated with their adhesiveness to thymic epithelial cells (TEC) in vitro. Blocking experiments with monoclonal antibody or peptides showed the following: (1) that the LDV rather than the REDV cell attachment motif in the IIIC segment of fibronectin is targeted by the 4 integrin during thymocyte/TEC adhesion; (2) that the RGD motif of the 120-kD fragment of fibronectin, a target for 5 integrin, has a secondary role in this adhesion; and (3) that the YIGSR cell attachment motif of the β1 chain of laminin/merosin recognized by a nonintegrin receptor is not used for thymocyte adherence. In conclusion, our results show that an upregulated set of receptors endows CD25+ precursors and cells up to the young DP stage with a high capability of interacting with thymic ECM components.

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Neoplastic thymic epithelial cells of human thymoma support T cell development from CD4− CD8− cells to CD4+ CD8+ cells in vitro

Clinical & Experimental Immunology ◽

10.1046/j.1365-2249.1998.00606.x ◽

1998 ◽

Vol 112 (3) ◽

pp. 419-426 ◽

Cited By ~ 19

Author(s):

Inoue ◽

Fujii ◽

Okumura ◽

Takeuchi ◽

Shiono ◽

...

Keyword(s):

T Cell ◽

Epithelial Cells ◽

T Cell Development ◽

Cell Development ◽

Thymic Epithelial Cells ◽

Cd8 Cells

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Role of Prolactin and Growth Hormone on Thymus Physiology

Developmental Immunology ◽

10.1155/1998/89782 ◽

1998 ◽

Vol 6 (3-4) ◽

pp. 317-323 ◽

Cited By ~ 39

Author(s):

Valéria De Mello-Coelho ◽

Wilson Savino ◽

Marie-Catherine Postel-Vinay ◽

Mireille Dardenne

Keyword(s):

Growth Hormone ◽

Epithelial Cells ◽

Cell Types ◽

Pituitary Hormones ◽

Thymic Epithelial Cells ◽

Double Positive ◽

Gh Treatment ◽

Thymic Hormone

Intrathymic T-cell differentiation is under the control of the thymic microenvironment, which acts on maturing thymocytes via membrane as well as soluble products. Increasing data show that this process can be modulated by classical hormones, as exemplified herein by prolactin (PRL) and growth hormone (GH), largely secreted by the pituitary gland.Both PRL and GH stimulate the secretion of thymulin, a thymic hormone produced by thymic epithelial cells. Conversely, low levels of circulating thymulin parallel hypopituitary states. Interestingly, the enhancing effects of GH on thymulin seem to be mediated by insulinlike growth factor (IGF-1) since they can be abrogated with anti-IGF-1 or anti-IGF-l-receptor antibodies. The influence of PRL and GH on the thymic epithelium is pleiotropic: PRL enhancesin vivothe expression of high-molecular-weight cytokeratins and stimulatesin vitroTEC proliferation, an effect that is shared by GH and IGF-1.Differentiating T cells are also targets for the intrathymic action of PRL and GH.In vivoinoculation of a rat pituitary cell line into old rats results in restoration of the thymus, including differentiation of CD4-CD8-thymocytes into CD4+CD8+cells. Furthermore, PRL may regulate the maintenance of thymocyte viability during the double-positive stage of thymocyte differentiation.Injections of GH into aging mice increase total thymocyte numbers and the percentage of CD3-bearing cells, as well as the Concanavalin-A mitogenic response and IL-6 production by thymocytes. Interestingly, similar findings are observed in animals treated with IGF-1. Lastly, the thymic hypoplasia observed in dwarf mice can be reversed with GH treatment.In keeping with the data summarized earlier is the detection of receptors for PRL and GH on both thymocytes and thymic epithelial cells. Importantly, recent studies indicate that both cell types can produce PRL and GH intrathymically. Similarly, production of IGF-1 and expression of a corresponding receptor has also been demonstrated.In conclusion, these data strongly indicate that the thymus is physiologically under control of pituitary hormones PRL and GH. In addition to the classical endocrine pathway, paracrine and autocrine circuits are probably implicated in such control.

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In vitro culture of human thymic epithelial cells in serum-free media

Apmis ◽

10.1111/j.1699-0463.1989.tb00500.x ◽

1989 ◽

Vol 97 (7-12) ◽

pp. 926-934 ◽

Cited By ~ 4

Author(s):

BIRGER CHRISTENSSON ◽

PETER BIBERFELD ◽

ROLAND GRAFSTRÖM ◽

GEORG MATELL

Keyword(s):

Epithelial Cells ◽

In Vitro Culture ◽

Thymic Epithelial Cells ◽

Serum Free ◽

Free Media

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Medium Calcium Concentration Determines Keratin Intermediate Filament Density and Distribution in Immortalized Cultured Thymic Epithelial Cells (TECs)

Microscopy and Microanalysis ◽

10.1017/s1431927605050282 ◽

2005 ◽

Vol 11 (4) ◽

pp. 283-292 ◽

Cited By ~ 1

Author(s):

Sandra S. Sands ◽

William D. Meek ◽

Jun Hayashi ◽

Robert J. Ketchum

Keyword(s):

Epithelial Cells ◽

Calf Serum ◽

Growth Conditions ◽

Thymic Epithelial Cells ◽

Culture Techniques ◽

Low Calcium ◽

High Calcium ◽

Primary Cell Lines ◽

Immortalized Cell

Isolation and culture of thymic epithelial cells (TECs) using conventional primary tissue culture techniques under conditions employing supplemented low calcium medium yielded an immortalized cell line derived from the LDA rat (Lewis [Rt1l] cross DA [Rt1a]) that could be manipulated in vitro. Thymi were harvested from 4–5-day-old neonates, enzymically digested using collagenase (1 mg/ml, 37°C, 1 h) and cultured in low calcium WAJC404A medium containing cholera toxin (20 ng/ml), dexamethasone (10 nM), epidermal growth factor (10 ng/ml), insulin (10 μg/ml), transferrin (10 μg/ml), 2% calf serum, 2.5% Dulbecco's Modified Eagle's Medium (DMEM), and 1% antibiotic/antimycotic. TECs cultured in low calcium displayed round to spindle-shaped morphology, distinct intercellular spaces (even at confluence), and dense reticular-like keratin patterns. In high calcium (0.188 mM), TECs formed cobblestone-like confluent monolayers that were resistant to trypsinization (0.05%) and displayed keratin intermediate filaments concentrated at desmosomal junctions between contiguous cells. Changes in cultured TEC morphology were quantified by an analysis of desmosome/membrane relationships in high and low calcium media. Desmosomes were significantly increased in the high calcium medium. These studies may have value when considering the growth conditions of cultured primary cell lines like TECs.

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