scholarly journals Interferons Mediate Terminal Differentiation of Human Cortical Thymic Epithelial Cells

2002 ◽  
Vol 76 (13) ◽  
pp. 6415-6424 ◽  
Author(s):  
Pierre-Olivier Vidalain ◽  
David Laine ◽  
Yona Zaffran ◽  
Olga Azocar ◽  
Christine Servet-Delprat ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Measles Virus ◽  
Present Report ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Induced Differentiation ◽  
Thymic Epithelium ◽  
Thymus Epithelial Cells

ABSTRACT In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-β) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-β induction. Finally, we demonstrated that recombinant IFN-α, IFN-β, or IFN-γ was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections.

scholarly journals Heterogeneity of thymic epithelial cell (TEC) keratins--immunohistochemical and biochemical evidence for a subset of highly differentiated TEC in the mouse.

1985 ◽  
Vol 33 (7) ◽  
pp. 687-694 ◽  
Author(s):  
J F Nicolas ◽  
W Savino ◽  
A Reano ◽  
J Viac ◽  
J Brochier ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
High Molecular Weight ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Small Subset ◽  
Thymic Epithelium ◽  
Differentiated Cells ◽  
Medullary Epithelial Cells

The mouse thymic epithelial network was studied using three different anti-keratin antibodies. One of these antibodies, KL1, exclusively recognized a small subset of medullary epithelial cells characterized by its content of a high molecular weight keratin (63 kD). Since epithelial differentiation is known to be associated with the acquisition of high molecular weight keratins, KL1-positive cells, which express the Ia antigen and secrete thymulin, may represent a subset of highly differentiated cells among mouse thymic epithelial cells (TEC). These data reflect the heterogeneity of the thymic epithelium and support the concept that distinct TEC subsets might provide the thymus with different microenvironments.

INDUCTION OF T-CELL DIFFERENTIATION IN VITRO BY THYMUS EPITHELIAL CELLS

1975 ◽  
Vol 249 (1 Thymus Factor) ◽  
pp. 492-498 ◽  
Author(s):  
Samuel D. Waksal ◽  
Irun R. Cohen ◽  
Harlan W. Waksal ◽  
Hartmut Wekerle ◽  
Ronald L. St. Pierre ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
T Cell Differentiation ◽  
Thymus Epithelial Cells

scholarly journals An in vitro system of T cell maturation-effect of cytokines and of thymic epithelial cells ♦ 865

1998 ◽  
Vol 43 ◽  
pp. 150-150
Author(s):  
Athena P Kourtis ◽  
Francis K Lee ◽  
Christian Ibegbu ◽  
Edmund Waller ◽  
Andre J Nahmias
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Cell Maturation ◽  
Thymic Epithelial Cells ◽  
In Vitro System ◽  
T Cell Maturation

Mouse embryonic stem cell-derived thymic epithelial cell progenitors enhance T-cell reconstitution after allogeneic bone marrow transplantation

Blood ◽  
2011 ◽  
Vol 118 (12) ◽  
pp. 3410-3418 ◽  
Author(s):  
Laijun Lai ◽  
Cheng Cui ◽  
Jingjun Jin ◽  
Zhifang Hao ◽  
Qiuhong Zheng ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cell ◽  
Allogeneic Bone Marrow Transplantation ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Allogeneic Bone ◽  
Thymic Involution

Abstract We have reported that mouse embryonic stem cells (mESCs) can be selectively induced in vitro to differentiate into thymic epithelial cell progenitors (TEPs). When placed in vivo, these mESC-derived TEPs differentiate into cortical and medullary thymic epithelial cells, reconstitute the normal thymic architecture, and enhance thymocyte regeneration after syngeneic BM transplantation (BMT). Here, we show that transplantation of mESC-derived TEPs results in the efficient establishment of thymocyte chimerism and subsequent generation of naive T cells in both young and old recipients of allo-geneic BM transplant. GVHD was not induced, whereas graft-versus-tumor activity was significantly enhanced. Importantly, the reconstituted immune system was tolerant to host, mESC, and BM transplant donor antigens. Therefore, ESC-derived TEPs may offer a new approach for the rapid and durable correction of T-cell immune deficiency after BMT, and the induction of tolerance to ESC-derived tissue and organ transplants. In addition, ESC-derived TEPs may also have use as a means to reverse age-dependent thymic involution, thereby enhancing immune function and decreasing infection rates in the elderly.

scholarly journals Doxycycline Protects Thymic Epithelial Cells from Mitomycin C-Mediated Apoptosis In Vitro via Trx2-NF-κB-Bcl-2/Bax Axis

2016 ◽  
Vol 38 (2) ◽  
pp. 449-460 ◽  
Author(s):  
Jun Wang ◽  
Ya Zhuo ◽  
Lei Yin ◽  
Hui Wang ◽  
Yanqiu Jiang ◽  
...  
Keyword(s):  
T Cell ◽  
Epithelial Cells ◽  
Mitomycin C ◽  
Mapk Signaling ◽  
Thymic Epithelial Cells ◽  
Cell Repertoire ◽  
Gm Csf ◽  
Induced Apoptosis ◽  
A Tec

Background/Aims: Age-associated and stress-induced involution of the thymus is accompanied by reduced numbers of thymic epithelial cells (TECs) and severe reduction in peripheral T cell repertoire specificities. These events seriously affect immune function, but the mechanisms involved are unclear. Our preliminary findings showed that doxycycline (Dox) could drive the proliferation of a TEC line (MTEC1 cells) partially via the MAPK signaling pathway. Dox can also up-regulate IL-6 and GM-CSF expression via the NF-κB and MAPK/ERK pathways. Herein, we investigate the effects and mechanisms used by Dox that protect against mitomycin C (MMC)-induced MTEC1 cell apoptosis. Methods: MTEC1 cells were treated with Dox, MMC, and Dox plus MMC for different amounts of time. The expression of Trx2, NF-κB, Bcl-2, and Bax proteins were then detected by western blotting. Results: Our findings show that Dox protects MTEC1 cells from MMC-induced apoptosis. Dox up-regulated the expression of Trx2 and promoted NF-κB phosphorylation. Meanwhile, Dox also increased the expression of Bcl-2, partially reduced the expression of Bax, and normalized the ratio of Bcl-2 to Bax. Conclusion: Dox exerts an anti-apoptosis function via the NF-κB-Bcl-2/Bax and Trx2-ASK1/JNK pathways in vitro. Therefore, Dox may represent a drug that could be used to attenuate thymic senescence, rescue thymic function, and promote T cell reconstitution.

scholarly journals Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny.

1983 ◽  
Vol 157 (3) ◽  
pp. 907-920 ◽  
Author(s):  
B F Haynes ◽  
M Robert-Guroff ◽  
R S Metzgar ◽  
G Franchini ◽  
V S Kalyanaraman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Epithelial Cells ◽  
Leukemia Virus ◽  
Thymic Epithelial Cells ◽  
Cortical Region ◽  
Cell Leukemia ◽  
Thymic Epithelium ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Using monoclonal antibody 12/1-2 against a 19,000-dalton human T cell leukemia virus (HTLV) protein (anti-p19), previously demonstrated to be reactive with HTLV-infected human cells, but not in numerous other uninfected cells, we found a reactive antigen to be expressed on the neuroendocrine component of human thymic epithelial cells but not on any other normal epithelial or neuroendocrine human tissues. Moreover, this reactive antigen is acquired on neuroendocrine thymic epithelium during thymic ontogeny--first appearing on fetal thymic epithelial cells between 8 and 15 wk gestation. While only a portion of thymic epithelial cells in the subcapsular cortical region of 15- and 24-wk fetal thymuses contained anti-p19+ epithelial cells, the entire subcapsular cortical region of newborn thymus epithelium was anti-p19+. By age 3 yr, normal subjects' entire subcapsular cortical and medullary thymic epithelium was anti-p19+. Using antibody against HTLV core protein, p24, and c-DNA probes for HTLV DNA, neither HTLV-specific p24 protein nor proviral DNA could be demonstrated in anti-p19+ thymic epithelial tissue. However, thymic epithelial extracts, disrupted HTLV extracts, as well as purified HTLV p19 antigen all inhibited the binding of anti-p19 antibody to thymic epithelium. Thus, anti-p19 may recognize a determinant on an HTLV-encoded 19,000-dalton structural protein that is shared by human thymic epithelium. Alternatively, anti-p19 defines a host encoded protein that is selectively expressed by normal thymic epithelium, and is induced to be expressed in HTLV-infected malignant T cells.

scholarly journals Lack of Foxp3 function and expression in the thymic epithelium

2007 ◽  
Vol 204 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Adrian Liston ◽  
Andrew G. Farr ◽  
Zhibin Chen ◽  
Christophe Benoist ◽  
Diane Mathis ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Epithelial Cells ◽  
Cell Population ◽  
Cell Lineage ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelium ◽  
Thymocyte Differentiation ◽  
Necessary And Sufficient

Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4+ T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells.

scholarly journals Measles Virus Infection Induces Terminal Differentiation of Human Thymic Epithelial Cells

1999 ◽  
Vol 73 (3) ◽  
pp. 2212-2221 ◽  
Author(s):  
Hélène Valentin ◽  
Olga Azocar ◽  
Branka Horvat ◽  
Rejane Williems ◽  
Robert Garrone ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Measles Virus ◽  
Terminal Differentiation ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Epithelial Cell Line ◽  
Epithelial Cell Differentiation

ABSTRACT Measles virus infection induces a profound immunosuppression that may lead to serious secondary infections and mortality. In this report, we show that the human cortical thymic epithelial cell line is highly susceptible to measles virus infection in vitro, resulting in infectious viral particle production and syncytium formation. Measles virus inhibits thymic epithelial cell growth and induces an arrest in the G0/G1 phases of the cell cycle. Moreover, we show that measles virus induces a progressive thymic epithelial cell differentiation process: attached measles virus-infected epithelial cells correspond to an intermediate state of differentiation while floating cells, recovered from cell culture supernatants, are fully differentiated. Measles virus-induced thymic epithelial cell differentiation is characterized by morphological and phenotypic changes. Measles virus-infected attached cells present fusiform and stellate shapes followed by a loss of cell-cell contacts and a shift from low- to high-molecular-weight keratin expression. Measles virus infection induces thymic epithelial cell apoptosis in terminally differentiated cells, revealed by the condensation and degradation of DNA in measles virus-infected floating thymic epithelial cells. Because thymic epithelial cells are required for the generation of immunocompetent T lymphocytes, our results suggest that measles virus-induced terminal differentiation of thymic epithelial cells may contribute to immunosuppression, particularly in children, in whom the thymic microenvironment is of critical importance for the development and maturation of a functional immune system.

scholarly journals Mechanisms of Igf2 inhibition in thymic epithelial cells infected by coxsackievirus CV-B4

2020 ◽  
Author(s):  
Hélène Michaux ◽  
Aymen Halouani ◽  
Charlotte Trussart ◽  
Chantal Renard ◽  
Hela Jaïdane ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Epithelial Cell Line ◽  
Central Tolerance ◽  
Coxsackievirus B4 ◽  
Stat3 Signaling

ABSTRACTEpidemiological studies have evidenced a link between type 1 diabetes (T1D) and infections by enteroviruses, especially with coxsackievirus B4 (CV-B4). CV-B4 is able to infect human and murine thymic epithelial cells (TECs) and, in a murine TEC line, we have shown that the diabetogenic strain CV-B4 E2 decreases transcription of insulin-like growth factor 2 gene (Igf2), coding for the self-peptide of the insulin family. Here we show that in CV-B4 infection of mice alters Igf2 transcripts isoforms in TECs, followed by a decrease of pro-IGF2 precursor in the thymus. CV-B4 infection of a murine TEC line decreases Igf2 P3 promoter activity by targeting the region −68 to −22 upstream of the transcription start site (TSS) whereas Igf2 transcripts stability is not affected, pointing towards a regulation of Igf2 transcription. Our data also show that CV-B4 decreases IL-6/STAT3 signaling in vitro. This study provides new knowledge about the regulation of intrathymic Igf2 transcription by CV-B4 and reinforces the hypothesis that CV-B4 infection of the thymus could break central self-tolerance of the insulin family by decreasing Igf2 transcription and IGF2 presentation in thymus epithelium.IMPORTANCECoxsackievirus B4 represents one of the most important environmental factors associated to type 1 diabetes, autoimmune disease for which no curative treatment exist. The diabetogenic strain Coxsackievirus B4 E2 was previously shown to decrease Igf2 expression, important player for central tolerance towards insulin, in a thymic epithelial cell line. The understanding of Igf2 regulation mechanisms during coxsackievirus B4 infection represents an interest for the understanding of central tolerance development but also for Igf2 transcriptional regulation itself, still poorly understood.Here we demonstrate that, some transcripts isoforms of Igf2 are also decreased in thymic epithelial cells in vivo. Moreover, we show that this decrease is induced by an alteration of specific regions of Igf2 P3 promoter and may be linked by a decrease of STAT3 signaling. In fine we hope that this work could lead to future therapies leading to reprogramming central tolerance towards β cells antigens via Igf2 expression.

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