scholarly journals Ontogeny of Rat Thymic Epithelium Defined by Monoclonal Anticytokeratin Antibodies

1990 ◽  
Vol 1 (2) ◽  
pp. 67-75 ◽  
Author(s):  
Miodrag Čolić ◽  
Suzana Jovanović ◽  
Milijana Vasiljevski ◽  
Aleksandar Dujić
Keyword(s):  
Monoclonal Antibodies ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
Postnatal Life ◽  
Immunoperoxidase Method ◽  
Simultaneous Presence ◽  
Thymic Epithelium ◽  
Large Panel ◽  
Ontogenetic Study

Ontogenetic study on the expression of cytokeratin (CK) polypeptides within particular subsets of rat thymic epithelial cells (TEC) has been performed by a large panel of anti-CK monoclonal antibodies (mAbs) using the streptavidin-biotin immunoperoxidase method. Simultaneous presence of two or more CK subunits in the same TEC has been demonstrated by double immunoflouorescence labeling. The obtained results showed that the expression of CK polypeptides in fetal and neonatal thymus differed from the adult patterns. The main difference was observed in expression of CK10, 18, and 19 polypeptides. During fetal ontogeny, CK10 and 18 are markers for most medullary TEC or a subset of medullary TEC, respectively, whereas CK19 is mainly a pan-TEC marker. In the adult animals, they are localized in the cortical and a subset of medullary TEC (CK18), subcapsular/perivascular and some medullary TEC (CK19), or in a subset of medullary TEC and Hasall’s corpuscles (HC) (CK10). The switch in their expression in the cortex was observed during the first two weeks of postnatal life.

scholarly journals Neuropeptides Exert Direct Effects on Rat Thymic Epithelial Cells in Culture

1998 ◽  
Vol 6 (1-2) ◽  
pp. 95-104 ◽  
Author(s):  
Gail M. Head ◽  
R. Mentlein ◽  
Birte Von Patay ◽  
J. E.G. Downing ◽  
Marion D. Kendall
Keyword(s):  
Epithelial Cells ◽  
Lucifer Yellow ◽  
Tritiated Thymidine ◽  
Single Cells ◽  
Thymic Epithelial Cells ◽  
Dye Coupling ◽  
Direct Effects ◽  
Adrenergic Agonist ◽  
Thymic Epithelium ◽  
Functional Aspects

To determine if major thymic neuropeptides and neurotransmitters can directly influence the functional activity of cultured rat thymic epithelium, neuropeptides and neurotransmitters were applied, and intercellular communication, proliferation, and thymulin secretion assessed. After injections of a mixture of lucifer yellow dextran (too large to pass gap junctions) and cascade blue (which does) into single cells, some neuropeptides decrease dye coupling: 0.1 mM GABA (P< 0.0001), 100 nM NPY (P< 0.0001), 100 nM VIP (P< 0.001), 100 nM CGRP (P< 0.001), 100 nM SP (P< 0.01), and 0.1 mM histamine (P< 0.01), whereas 0.1 mM 5-HT, mM acetylcholine, and 1μM isoproterenol (β-adrenergic agonist) had no effect. Proliferation (incorporation of tritiated thymidine) was increased by CGRP (P= 0.004) and histamine (P< 0.02), but decreased by isoproterenol (P= 0.002), 5-HT (P= 0.003), and acetylcholine (P< 0.05). The percentage of multinucleate cells was decreased after isoproterenol (2.5%), and increased after 5-HT (21.3%), GABA (15%), and histamine (15.1%). Compared to controls, thymulin in the supernatant was decreased after challenge with acetylcholine (52%), isoproterenol (71%), 5-HT (73%), and histamine (84%). This study demonstrates direct effects of neuropeptides and neurotransmitters on functional aspects of cultured thymic epithelial cells.

scholarly journals Developmental studies on expression of monoclonal antibody-defined cytokeratins by thymic epithelial cells from normal and autoimmune mice.

1988 ◽  
Vol 36 (9) ◽  
pp. 1123-1129 ◽  
Author(s):  
W Savino ◽  
M Dardenne
Keyword(s):  
Monoclonal Antibodies ◽  
Epithelial Cells ◽  
Thymic Epithelial Cells ◽  
High Dose ◽  
Fetal Life ◽  
Developmental Studies ◽  
Complex Products ◽  
Histocompatibility Complex ◽  
Cytokeratin Expression

A major component of the thymic microenvironment is a network of thymic epithelial cells (TEC) which are able to express class II major histocompatibility complex products and to secrete thymic hormones. In the present investigation, we used a panel of anti-cytokeratin (CK) antibodies to establish distinct cytokeratin-defined TEC subsets. Four subpopulations were identified. One, in the cortex, is defined by anti-CK8 and anti-CK18 monoclonal antibodies (MAb). The other three subsets are medullary, two minor ones respectively reactive with anti-CK19 and KL1 monoclonal antibodies (the latter being specific for CK3 and 10), and a major one characterized by negative reaction with the above-mentioned MAb but strongly positive after labeling with a polyclonal (and polyspecific) anti-keratin immunoserum. Ontogenetic studies revealed that the CK8+/18+ TEC subset is the first to be detected in fetal life. Moreover, the numbers of CK3/10+ cells and CK19+ cells decrease in aging normal mice, a phenomenon that seems to occur early in autoimmune mice. We also observed that these two medullary TEC subsets are sensitive to high-dose in vivo treatment with hydrocortisone, which stimulates a dramatic increase in CK3/10+ cells and a certain decrease in CK19+ cells. Our results indicate that a number of mouse TEC subsets can be distinguished by cytokeratin expression. Such a strategy can be applied to analyze TEC sensitivity to drugs and might also be useful to further understanding of differential TEC function regarding intrathymic T-cell differentiation.

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.

scholarly journals Human Thymic Epithelial Cells in Serum-Free Culture: Nature and Effects on Thymocyte Cell Lines

1992 ◽  
Vol 2 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Carsten Ropke ◽  
Jette Elbroend
Keyword(s):  
Monoclonal Antibodies ◽  
Epithelial Cells ◽  
Cell Types ◽  
Thymic Epithelial Cells ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Factors ◽  
Serum Free ◽  
Functional Activities ◽  
Thymocyte Proliferation

Thymic epithelial cells (TEC) have been cultured for several months and/or for 4 to 5 transfers in a growth factor-defined serum-free medium without concurrent growth of other cell types. The use of monoclonal antibodies andαMAM-6 indicated that the majority of TEC were of medullary origin. The vast majority of cells were positive for LFA-3 and class I, and class II expression, was low or absent. Supernatants from the cultures were shown to contain IL-1ß, IL-6, and M-CSF. Coculture of cloned subpopulations of thymocytes and TEC showed effects of TEC and of secreted ILs on thymocyte proliferation. High percentages of TEC were able to bind DN, DP, or SP thymocyte populations, partly via CD2-LFA-3 adhesion. Thus, it is possible to culture TEC without unknown serum factors and with maintenance of functional activities.

scholarly journals Contrasting models of promiscuous gene expression by thymic epithelium

2005 ◽  
Vol 202 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Geoffrey O. Gillard ◽  
Andrew G. Farr
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Broad Spectrum ◽  
Alternative Model ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Thymic Epithelium ◽  
Medullary Thymic Epithelial Cells ◽  
Promiscuous Gene Expression ◽  
Self Antigens

Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue- restricted self-antigens (TRAs), which are required for the development of central tolerance. A new study suggests that TRA expression is a specialized property of terminally differentiated mTECs. However, as discussed here, an alternative model—whereby TRA expression is regulated by conserved developmental programs active in developing mTECs—may be equally plausible.

scholarly journals Thymus Inception: Molecular Network in the Early Stages of Thymus Organogenesis

2020 ◽  
Vol 21 (16) ◽  
pp. 5765
Author(s):  
Marta Figueiredo ◽  
Rita Zilhão ◽  
Hélia Neves
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Thymic Epithelial Cells ◽  
Environmental Cues ◽  
Special Focus ◽  
Thymic Epithelium ◽  
Stromal Microenvironment ◽  
Pharyngeal Endoderm

The thymus generates central immune tolerance by producing self-restricted and self-tolerant T-cells as a result of interactions between the developing thymocytes and the stromal microenvironment, mainly formed by the thymic epithelial cells. The thymic epithelium derives from the endoderm of the pharyngeal pouches, embryonic structures that rely on environmental cues from the surrounding mesenchyme for its development. Here, we review the most recent advances in our understanding of the molecular mechanisms involved in early thymic organogenesis at stages preceding the expression of the transcription factor Foxn1, the early marker of thymic epithelial cells identity. Foxn1-independent developmental stages, such as the specification of the pharyngeal endoderm, patterning of the pouches, and thymus fate commitment are discussed, with a special focus on epithelial–mesenchymal interactions.

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 Is There an Interspecific Diversity of the Thymic Microenvironment?

1993 ◽  
Vol 3 (2) ◽  
pp. 123-135 ◽  
Author(s):  
Lucia Renata Meireles de Souza ◽  
Valeria Trajano ◽  
Wilson Savino
Keyword(s):  
Extracellular Matrix ◽  
Monoclonal Antibodies ◽  
Comparative Study ◽  
Mammalian Species ◽  
Thymic Epithelial Cells ◽  
General Phenomenon ◽  
Thymic Epithelium ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Interspecific Diversity

Thymic epithelial cells (TEC) heterogeneity suggests the existence of functional subsets. Anti-cytokeratin (Anti-CK) monoclonal antibodies (MAb), markers of epithelial differentiation, have been used to detect TEC subsets in rodents and humans. These MAb revealed a different topography of CK-defined TEC subsets in mice and humans, leading us to carry out a comparative study of mammalian thymuses. Our study showed that the distribution pattern of cytokeratins in the thymic epithelium is complex and unique, with coexpression of CK typical of simple and stratified epithelia. Moreover, we demonstrated an interspecific diversity of CK expression within the thymic lobules. Interestingly, such diversity was not a general phenomenon for the expression of any thymic microenvironmental proteins, because the location of extracellular matrix components was essentially similar in the mammalian species studied.

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