BACKGROUND: Moderate acute malnutrition (MAM) affects millions of children, increasing their risk of dying from infections. Thymus atrophy may be a marker of malnutrition-associated immunodeficiency, but factors associated with thymus size in children with MAM are unknown, as is the effect of nutritional interventions on thymus size.. METHODS: Thymus size was measured by ultrasound in 279 children in Burkina Faso with MAM, diagnosed by low mid-upper arm circumference (MUAC) and/or low weight-for-length z-score (WLZ), who received 12 weeks treatment with different food supplements as part of a randomized trial. Correlates of thymus size and of changes in thymus size after treatment, and after another 12 weeks of follow-up were identified.. RESULTS: Thymus size correlated positively with age, anthropometry and blood haemoglobin, and was smaller in children with malaria. Children with malnutrition diagnosed using MUAC had a smaller thymus than children diagnosed based on WLZ. Thymus size increased ...
does not cause any significant changes in the body.. Numerous attempts to isolate the hormone of the thymus are still unsuccessful.True, Bomskov and Sladovic received from the thymus gland lipoid extract containing allegedly hormone that causes a decrease in glycogen in the liver and the heart of the experimental animal and the rise in blood sugar.. These data were confirmed and further developed by many scientists.They found that the lipoid thymus extract contains at least four fractions having different chemical composition and having unequal effect on the metabolism.The fraction containing mainly sterols, reduce glycogen content in the liver, while the fraction consisting essentially of fosfotidov increases its contents.. After partial resection of the thymus gland in animals its remnants, according to many researchers, are not subject to compensatory hyperplasia.Therefore, it should be recognized that the thymus gland does not meet the classical criteria of an endocrine organ.. However, ...
In this work, the interaction between a rat cortical thymic epithelial cell (TEC) line (R-TNC.1) with nursing activity and thymocytes as well as BWRT 8 thymocyte hybridoma (TH) cells has been studied. The R-TNC.1 cell line significantly bound thymocytes and TH. Binding was stronger during the first 30 min of cell incubation and was followed by a progressive deadhesion. Among adherent thymocytes the proportion of apoptotic cells increased with culture time which was a consequence of higher capacity of the line for binding of apoptotic than viable cells and induction of apoptosis in a subset of adherent thymocytes. Emperiopolesis activity of this thymic nurse cell (TNC) line was manifested by engulfment of thymocytes as well as TH cells. A subset of viable intra-TNC thymocytes has been triggered to die by apoptosis, whereas other internalized thymocytes have been stimulated to proliferate, as measured by an increase in the percentage of cells in mitosis and higher incorporation of bromodeoxyuridine (BrdU)
I am the Spirit of Purification I protect the life and this temple from harm I bring heaven and earth together as one I give assurance to my world that all is well THE ANGELIC GLAND OF THE THYMUS This graphic by artist David Stefaniak depicts the young thymus gland inside the upper chest cavity.…
Thymus function depends on the epithelial compartment of the thymic stroma. Cortical thymic epithelial cells (cTECs) regulate T cell lineage commitment and positive selection, while medullary (m) TECs impose central tolerance on the T cell repertoire. During thymus organogenesis, these functionally distinct sub-lineages are thought to arise from a common thymic epithelial progenitor cell (TEPC). The mechanisms controlling cTEC and mTEC production from the common TEPC are not however understood. Here, we show that emergence of the earliest mTEC lineage-restricted progenitors requires active NOTCH signaling in progenitor TEC and that, once specified, further mTEC development is NOTCH-independent. In addition, we demonstrate that persistent NOTCH activity favors maintenance of undifferentiated TEPC at the expense of cTEC differentiation. Finally, we uncover a cross-regulatory relationship between NOTCH and FOXN1, a master regulator of TEC differentiation. These data establish NOTCH as a potent ...
Thymus gland tissue. Light micrograph of a transverse section through tissue from the thymus gland, part of the lymphoid system. The black areas are the thymic cortex, which produces lots of lymphocytes. The grey areas, the thymic medulla, produce less lymphocytes. In-between are blood vessels (pink). This gland is located in the throat. Its role is to produce and mature T-lymphocytes (a specialised form of white blood cell), as well as other, more basic lymphocytes. It also controls the development of lymph nodes and the spleen. Magnification: x2 when printed 10 centimetres wide. - Stock Image C011/8386
This video describes about thymus gland. The thymus gland is a lobular structure located on the dorsal side of the heart and the aorta. The thymus plays a major role in the development of the ...
Lymphopoiesis was studied in 3-month-old normal C57Bl mice and in 3-month-old C57Bl mice carrying from 12 to 48 C57Bl thymus grafts using tritiated thymidine labeling.. Thymus graft lymphopoiesis was found to be identical with that of normal thymus tissue and the presence of thymus grafts was found to have no influence on host thymus lymphopoiesis.. No evidence was found that the massive amounts of thymus graft tissue in the mice affected any parameter of host lymph node lymphopoiesis nor was any evidence detected for the migration of thymic lymphocytes from these massive deposits of thymus graft tissue either to host lymph nodes and blood or to other organs in the host animal.. It is concluded that the majority of small lymphocytes produced in the thymus and thymus graft tissue do not migrate from these tissues but die locally at the end of their intrathymic life span of 3 to 4 days.. ...
Thymic T cell development is dependent on a specialized epithelial microenvironment mainly composed of cortical and medullary thymic epithelial cells (TECs). The molecular programs governing the differentiation and maintenance of TECs remain largely unknown. Wnt signaling is central to the development and maintenance of several organ systems but a specific role of this pathway for thymus organogenesis has not yet been ascertained. In this report, we demonstrate that activation of the canonical Wnt signaling pathway by a stabilizing mutation of beta-catenin targeted exclusively to TECs changes the initial commitment of endodermal epithelia to a thymic cell fate. Consequently, the formation of a correctly composed and organized thymic microenvironment is prevented, thymic immigration of hematopoietic precursors is restricted, and intrathymic T cell differentiation is arrested at a very early developmental stage causing severe immunodeficiency. These results suggest that a precise regulation of canonical
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs). These ClonoTECs are EpCAM+MHCII-Foxn1lo cells that lack traits of mature cTECs or mTECs but co-express stem-cell markers, including CD24 and Sca-1. Supportive of their progenitor identity, ClonoTECs reintegrate within native thymic microenvironments and generate cTECs or mTECs in vivo. Strikingly, the frequency of cTECs with the potential to generate ClonoTECs wanes between the postnatal and young adult immunocompetent thymus, but it is sustained in alymphoid Rag2-/-Il2rg-/- counterparts. ...
The thymic epithelium forms specialized niches to enable thymocyte differentiation. While the common epithelial progenitor of medullary and cortical thymic epithelial cells (mTECs and cTECs) is well defined, early stages of mTEC lineage specification have remained elusive. Here, we utilized in vivo targeting of mTECs to resolve their differentiation pathways and to determine whether mTEC progenitors participate in thymocyte education. We found that mTECs descend from a lineage committed, podoplanin (PDPN)-expressing progenitor located at the cortico-medullary junction. PDPN(+) junctional TECs (jTECs) represent a distinct TEC population that builds the thymic medulla, but only partially supports negative selection and thymocyte differentiation. Moreover, conditional gene targeting revealed that abrogation of alternative NF-κB pathway signaling in the jTEC stage completely blocked mTEC development. Taken together, this study identifies jTECs as lineage-committed mTEC progenitors and shows that ...
Studies of the most immature T cell progenitors in the human thymus have been hampered by the lack of markers and assays that define these cells. In this report we used a novel human fetal thymic organ culture system to determine the potential of T cell precursors isolated from human postnatal thymus, to differentiate into CD3+ thymocytes, and to investigate early stages of human T cell development. It was found that thymocytes that lack the markers CD3, CD4, and CD8 (triple negative [TN]) can differentiate in an allogeneic organotypic thymic culture. The capacity of TN thymocytes to differentiate was exclusively confined to the CD34+ population. CD34- TN thymocytes failed to differentiate in this system. In contrast, cloned lines of CD3- thymocytes could only be established from CD34- TN thymocytes. Five subsets of CD3- thymocytes were found with the following phenotype: CD1-TN, CD1+TN, CD1+CD4+CD8-, CD1+CD4+CD8 alpha+ beta-, and CD1+CD4+CD8 alpha beta+. These subpopulations expressed ...
The epithelial cells of the Hassalls corpuscles in 11 human thymus glands (nine cases of myasthenia gravis and two glands from patients undergoing surgical correction of congenital heart disease) have been examined by electron microscopy. In every instance the epithelial cells have the cytoplasmic organelle complex necessary for `export-type secretory activity and in addition contain large numbers of membrane-limited small spheroidal secretion granules.. Hassalls corpuscles are avascular anatomical units and a pericorpuscular zone, at least 50 μm broad, is also without blood vessels.. It is therefore suggested that the secretory product(s) of the corpuscular epithelial cells has a purely intrathymic function.. ...
TY - JOUR. T1 - Determination of thymic function direct from peripheral blood. T2 - A validated modification to an established method. AU - Lorenzi, A. R.. AU - Patterson, Angela Margaret. AU - Pratt, A.. AU - Jefferson, M.. AU - Chapman, C. E.. AU - Ponchel, F.. AU - Isaacs, J. D.. PY - 2008/12/31. Y1 - 2008/12/31. N2 - The thymus contributes naive, self MHC reactive, self tolerant T cells to the peripheral immune system throughout life, albeit with a log-linear decline with age. Quantification of thymic function is clinically relevant in the setting of lymphoablation, but a phenotypic marker distinguishing recent thymic emigrants from long lived naive T cells remains elusive. T cell receptor excision circles (TREC) are present in thymocytes exiting the thymus and quantification of the most frequent of these, the delta rec-Psi J alpha rearrangement has been widely used as a measure of recent thymic function. However, interpretation of results presented as TREC per cell has been criticised on ...
The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC
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The thymus is the major site for the production of T cells in vertebrates. The cellular components of the thymus can be divided into two broad groups. Lymphoid cells are derived from bone marrow stem cells. This group of cells includes thymocytes, which are the major cellular component of the thymus. The other group, collectively known as stromal cells, develops mostly from epithelial cells derived from endoderm of the third pharyngeal pouch, ectoderm of the corresponding brachial clefts, and mesoderm from the pharyngeal arch. Cellular interaction between lymphoid cells and stromal cell-derived signals is required to support T cell development.. A major lab interest is in the identification of modulators of thymus function and T cell development. Because of the interdependence between lymphoid and stromal cells, both cell types are involved in the control of thymus function. However, until recently, it was not appreciated that stromal cells appear to play a major role in regulation of thymus ...
Do you know that on the body, every person has a point of happiness? And to search for it for a long time it is not necessary, it is a thymus, or thymus gland. It is located at the base of the sternum, two fingers below the clavicle
The thymus constitutes the primary lymphoid organ responsible for the generation of naive T cells. Its stromal compartment is largely composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiologic process. The precise cellular and molecular mechanisms underlying thymic senescence are, however, only incompletely understood. Here, we demonstrate that TGF-beta signaling in thymic epithelial cells exerts a direct influence on the cells capacity to support thymopoiesis in the aged mouse as the physiologic process of thymic senescence is mitigated in mice deficient for the expression of TGF-beta RII on thymic epithelial cells. Moreover, TGF-beta signaling in
Intact Thymus capsules provide a freeze-dried form of bovine thymus to support immune health. The thymus is a small, irregular-shaped gland in the top part of the chest, just under the breastbone and between the lungs. It is located in an area of the body called the mediastinum. The thymus is part of both the lymphatic system and the endocrine system. The thymus makes T cells (T lymphocytes) that travel throughout the body to help fight infection, disease and foreign substances. The thymus also makes hormones to help T cells develop and keep the immune system working properly. Lymphocytes travel from the bone marrow to the thymus, where they mature into T cells. Once T cells mature, they are able to leave the thymus and enter the blood so they can boost the immune system.* Directions: ...
T cell development is under tight control of the thymic microenvironment. In turn, the integrity of the thymic microenvironment depends on the physical presence of developing T lymphocytes, a phenomenon designated thymic crosstalk. We previously reported, using a novel mouse strain which has defects in both the thymic medina and cortex, that the induction of thymic cortex by bone marrow (BM) or fetal liver-derived T cell progenitors could be achieved on day 16 or 17 of gestation, but could not be induced in adulthood. Here, we further define the time window for this induction by prothymocytes. We first show that the induction of thymic cortex can be achieved during the neonatal stage. In 2 to 4 day post-partal neonates, BM injection could fully reconstituted the thymic structure and T cell compartments. Mice more than 4 days old showed decreased susceptibility to reconstitution. After 8 days, the susceptibility diminished. Next, we tested whether the induction could be obtained by prothymocytes
TY - JOUR. T1 - Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers. AU - Milivojevic,Verica. AU - Ansell,Emily. AU - Simpson,Christine. AU - Siedlarz,Kristen M.. AU - Sinha,Rajita. AU - Fox,Helen C.. PY - 2017. Y1 - 2017. N2 - Background: Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of this study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the ...
The thymus gland is in the chest between the lungs. It makes white blood cells (T lymphocytes) which are part of the immune system and help fight infection.
Functions of thymus gland include producing and processing T-cells which find and attack foreign bodies. Also learn the disorders when it cant function properly.
Thymic involution is thought to be an important factor of age related immunodeficiency. Understanding the molecular mechanisms of human thymic senescence may lead to the discovery of novel therapeutic approaches aimed at the reestablishment of central and peripheral T cell repertoire. As an initial approach, here we report that the decline of human thymic FOXN1 transcription correlates with age, while other genes, DLL1, DLL4 and WNT4, essential for thymopoiesis, are constitutively transcribed. Using a human thymic epithelial cell line (hTEC), we show that FOXN1 expression is refractory to signals that induce FOXN1 transcription in primary 3D culture conditions and by stimulation of the canonical WNT signaling pathway. Blockage of FOXN1 induceability in the hTEC line may be mediated by an epigenetic mechanism, the CpG methylation of the FOXN1 gene. We showed a suppression of FOXN1 transcription both in cultured human thymic epithelial cells and in the aging thymus. We hypothesize that the underlying
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. The thymus is composed of two identical lobes and is located anatomically in the anterior superior mediastinum, in front of the heart and behind the sternum. Histologically, each lobe of the thymus can be divided into a central medulla and a peripheral cortex which is surrounded by an outer capsule. The cortex and medulla play different roles in the development of T cells. Cells in the thymus can be divided into thymic stromal cells and cells of hematopoietic origin (derived from bone marrow resident hematopoietic stem cells). Developing T cells are referred to as thymocytes and are of hematopoietic origin. Stromal cells include epithelial cells of the thymic cortex and medulla, and dendritic cells. The thymus provides an inductive environment for development of T cells from ...
The CD4 and CD8 molecules are involved in T cell differentiation and activation. Nevertheless, efficient thymic maturation of helper T cells has been shown in the absence of the CD4 molecule. These CD4-deficient helper T cells expressed alpha beta-TCR and were able to control Leishmania infections and to mediate Ab class switch. Using mice deficient for the CD8 alpha-chain, we investigated whether a similar cytotoxic T cell population was generated in the absence of the CD8 coreceptor. A CD8-deficient cytotoxic T cell population corresponding to the described CD4-deficient helper T cell population was virtually absent both functionally and physically. These results support the idea that thymic maturation is asymmetrical and strongly biased toward the helper phenotype. ...
Rat Thymus Endothelial Cells from Creative Bioarray are isolated from thymus tissue of 6-8 week old laboratory Sprague-Dawley rat. Rat Thymus Endothelial Cells are grown in T75 tissue culture flasks pre-coated with gelatin-based coating solution for 2 min and incubated in Creative Bioarray Culture Complete Growth Medium generally for 3-7 days. Cultures are then expanded. Prior to shipping, cells at passage 3 are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 1x10^6 cells per ml and is delivered frozen. The method we use to isolate endothelial cells was developed based on a combination of established and our proprietary methods. These cells are pre-coated with PECAM-1 (CD31) antibody, following the application of magnetic beads pre-coated with secondary antibody ...
The peripheral naive T-cell pool is generally thought to consist of a subpopulation of recent thymic emigrants (RTE) and a subpopulation of mature naive (MN) T cells with different dynamics. Thymus transplantation and adoptive transfer studies in mice have provided contradicting results, with some studies suggesting that RTE are relatively short-lived cells, while another study suggested that RTE have a survival advantage. We here estimate the death rates of RTE and MN T cells by performing both thymus transplantations and deuterium labeling experiments in mice of at least 12 weeks old, an age at which the size of the T-cell pool has stabilized. For CD4+ T cells, we found the total loss rate from the RTE compartment (by death and maturation) to be 4-fold faster than that of MN T cells. We estimate the death rate of CD4+ RTE to be 0.046 per day, which is 3-fold faster than the total loss rate from the MN T-cell compartment. For CD8+ T cells, we found no evidence for kinetic differences between RTE and MN
However, the scarcity of donor organs means many people will not survive the wait for transplantation, said Dr. Lagasse, whose lab is at the McGowan Institute. Cell therapies are being explored, but introducing cells into tissue already ravaged by disease decreases the likelihood of successful engraftment and restoration of function.. In the study, his team tested the possibility of using lymph nodes, which are abundant throughout the body and have a rich blood supply, as a new home for cells from other organs in what is called an ectopic transplant.. They injected healthy liver cells from a genetically-identical donor animal into lymph nodes of mice at various locations. The result was an enlarged, liver-like node that functioned akin to the liver; in fact, a single hepatized lymph node rescued mice that were in danger of dying from a lethal metabolic liver disease. Likewise, thymus tissue transplanted into the lymph node of mice that lacked the organ generated functional immune systems, ...
Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB-ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis.
10.1055/b-0034-87953 Thorax, Mediastinum, Heart, and Great Vessels: Thymus Size from 0 to 2 Years of Age Material and Methods Mediastinal ultrasonography was performed in 151 infants (79 boys and 72 girls; Table 6.2 ). All children were healthy and had no stress factors affecting their thymic size. The maximum transverse diameter, right lobe AP, and…
NaturalNews) Biologists know that the thymus gland shrinks rapidly after puberty, but they have been unable to explain why this important gland turns to fat so quickly as people age. New research suggests that most peoples thymuses are missing some very important food-based antioxidants. If given the right amount of antioxidants, including Vitamin C and the enzyme catalase, the thymus can age more gracefully, keeping the immune system young and strong.. Exercising the thymus and giving it the right nutritional components gives it the capability to fight off pathogens into old age. Instead of retraining the immune system using synthetic vaccine chemicals and lab-grown viruses, healthy people can exercise their internal organs against all pathogens. They can let their intelligent natural defenses within their own thymus gland go to work. Research shows that if the thymus is given the right food-based antioxidants, it can thrive, keeping peoples immune systems young and strong as they age.. ...
Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes
The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus, and have been recently implicated in the central tolerance. In Foxn1lacZmutant mice, which undergo premature thymic involution beginning 1 week after birth, T committed progenitors were progressively reduced, however, thymic B cells started to increase at 1 week and transiently formed a peak at 3-4 weeks. These increased B cells were developed from neonatal derived BM progenitors possessing a high B potential, were originally generated in the thymus. Most of them showed CD19loB220loCD24hiCD43+/−IgM−progenitor phenotype with increased expression of Ly51 but decrease of CD25 accumulating at pre-B-II stage. These B progenitors showed a delayed down-regulation of Lin28b, an impaired up-regulation of Let-7 with an increased expression of Arid3a. However the treatment of these progenitor B cells with Vitamin D3 might up-regulate Let-7 and down-regulate Arid3 ...
A central question in T cell development is what makes cortical thymocytes respond to stimulation in a qualitatively different way than any other thymocyte subset. Part of the answer is that AP-1 function changes drastically at two stages of T cell development. It undergoes striking down-regulation as thymocytes differentiate from immature, CD4^-CD8^- double-negative (DN) TCR^- thymocytes to CD4^+CD8^+ double-positive (DP) TCR^(lo) cortical cells, and then returns in the cells that mature to TCR^(high), CD4^+CD8^- or CD4^-CD8^+ single-positive (SP) thymocytes. At all three stages, the jun family mRNAs can be induced similarly. However, we demonstrate that DP cortical thymocytes are specifically impaired in c-fos and fosB mRNA induction, even when stimuli are used that optimize survival of the cells and a form of in vitro maturation. fra-2 expression is induction independent but much lower in DP cells than in the other subsets. Overall Fos family protein induction accordingly is severely ...
Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance by expressing peripheral-tissue antigens. These antigens may be transferred to and presented by dendritic cells (DCs). Therefore, it is unclear whether mTECs, in addition to being an antigen reservoir, also serve a mandatory function as antigen-presenting cells. Here we diminished major histocompatibility complex (MHC) class II on mTECs through transgenic expression of a designer microRNA specific for the MHC class II transactivator CIITA (called C2TA here). This resulted in an enlarged polyclonal CD4+ single-positive compartment and, among thymocytes specific for model antigens expressed in mTECs, enhanced selection of regulatory T cells (Treg cells) at the expense of deletion. Our data document an autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4+ T cell tolerance and support an avidity model of Treg cell development versus deletion.
The thymus is the second fundamental organ of the immune system after the bone marrow; it is the essential for T cell maturation and repertoire selection. The function of the thymus critically depends on the thymic epithelium, which is structured in two distinct regions: The cortex and the medulla. The knowledge about molecular mechanisms involved in thymus development is limited. However, some evidences suggest that the Hox, Pax, Six, Eya, Gcm2, FGFs and Foxn1 are key players in thymus organogenesis. Foxn1 is essential for thymic epithelial cell development but its exact role is still unknown. The null mutation in the transcription factor Foxn1 generates the nude phenotype of athymia and hairlessness. The aim of our laboratory is to better understand thymus development and specially focuses on the Foxn1 function. The aim of this project is then to investigate target genes and transcription partners of Foxn1 as a transcriptional factor. As a transcription factor, Foxn1 protein should be able to ...
TY - JOUR. T1 - Potential applications of growth hormone in promoting immune reconstitution. AU - Welniak, Lisbeth. AU - Sun, Rui. AU - Murphy, William J. PY - 2002. Y1 - 2002. N2 - With the increasing use of bone marrow transplantation, (BMT) in cancer and in the advent of AIDS, it has been realized that successful reconstitution of the immune system of the adult is of paramount concern. Naive T cell production in the host requires T cell development in the thymus of the adult. Due to the impairment of thymus function with age, there has been renewed interest in utilizing neuroendocrine hormones (i.e. growth hormone or GH) to restore thymopoietic function. GH has been previously demonstrated to improve T cell function and affect thymopoiesis in mice. Recent studies indicate that GH is not an obligate growth factor for thymopoiesis but instead acts to counteract the effects of stress on the thymus. Thus, GH may be of potential use to enhance thymus function and T cell repopulation, particularly ...
This video describes about thymus gland. The thymus gland is a lobular structure located on the dorsal side of the heart and the aorta. The thymus plays a major role in the development of the ...
Progesterone receptors in rat thymus.: Tritiated promegestone ([3H]R5020) is bound with high affinity in cytosol prepared from the thymus gland of both male and
The thymus is an evolutionarily ancient primary lymphoid organ common to all vertebrates in which T cell development takes place. Failing thymus function is associated with immunodeficiency and/or autoimmunity. In this volume, leading experts provide a comprehensive overview of recent advances in thymopoiesis research. The chapters cover the development of the thymic epithelial microenvironment, address the formation of a diverse and self-tolerant repertoire of T cell receptors as the basis for cellular immunity, discuss the mechanisms by which progenitor cells colonize the thymus and detail the molecular basis for T lineage decisions. The reviews illustrate the important role of the multifaceted process of thymopoiesis for adaptive immunity ...
Data suggest that while antigen presenting function is relatively well preserved during the ageing process [5], lymphocyte function is perturbed, characterised by depression of both cellular and humoral immunity. Accordingly, to begin to address how ageing influences immunity, a focus on lymphocyte biology seems a good starting point. For example, over the decades numerous studies have reported altered production of T cell progenitors, reductions in the generation of naïve T cells, ageing of resting and clonally expanding cells, and in particular disrupted intracellular signalling leading to perturbations in cytoskeleton reorganisation and cell migration (reviewed in [6]). In this issue, Goronzy and Weyand begin by exploring how the dynamics of T cell repertoire diversity promote the expansion of effector cells [7]. Through an analysis of the expression of T cell receptor excision circles as surrogate markers of recent thymic emigrants, together with assays of telomerase activity, they have ...
Rabbit Thymus Endothelial Cells from Creative Bioarray are isolated from thymus tissue of New Zealand White Rabbit. Rabbit Thymus Endothelial Cells are grown in T25 tissue culture flasks pre-coated with gelatin-based coating solution for 2 min and incubated in Creative Bioarray Culture Complete Growth Medium generally for 3-7 days. Cultures are then expanded. Prior to shipping, cells are detached from flasks and immediately cryo-preserved in vials. Each vial contains at least 1x10^6 cells per ml and are delivered frozen. The method we use to isolate endothelial cells was developed based on a combination of established and our proprietary methods. These cells are pre-coated with PECAM-1 antibody, following the application of magnetic pre-coated with secondary antibody ...
Complete DiGeorge anomaly (cDGA) is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In complete DiGeorge subjects, thymus transplantation with and without immunosuppression has resulted in diverse T cell development and good T cell function. The purpose of this Phase I/II study is to continue thymus transplantation safety and efficacy research for the treatment of complete DiGeorge anomaly. Until thymus transplantation is FDA approved as standard care for DiGeorge anomaly, research study participation is the only means by which a patient may have access to this potentially life-saving procedure.. This protocol includes 4 groups: one for subjects who do not require immunosuppression; and 3 immunosuppression groups for subjects with different T cell function levels to be suppressed adequately.. Eligible subjects undergo thymus transplantation and an allograft biopsy. Protocol specified studies continue ...
TY - JOUR. T1 - MicroRNAs Regulate Thymic Epithelium in Age-Related Thymic Involution via Down-or Upregulation of Transcription Factors. AU - Xu, Minwen. AU - Zhang, Xiaoli. AU - Hong, Ruiyun. AU - Su, Dong Ming. AU - Wang, Liefeng. N1 - Funding Information: This work was partially supported by grants from the Higher Education Foundation of Jiangxi Provincial (KJLD2090), the Natural Science Foundation of Jiangxi Province (20132BAB205032), and the National Natural Science Foundation of China (31260279 and 31660256) to Liefeng Wang. Publisher Copyright: © 2017 Minwen Xu et al.. PY - 2017. Y1 - 2017. N2 - Age-related thymic involution is primarily induced by defects in nonhematopoietic thymic epithelial cells (TECs). It is characterized by dysfunction of multiple transcription factors (TFs), such as p63 and FoxN1, and also involves other TEC-associated regulators, such as Aire. These TFs and regulators are controlled by complicated regulatory networks, in which microRNAs (miRNAs) act as a key ...
Complete DiGeorge anomaly is a congenital disorder characterized by athymia. Without successful treatment, children remain immunodeficient and usually die by age 2 years. In infants with complete DiGeorge anomaly and no T cells, thymus transplantation without immunosuppression resulted in diverse T cell development and good T cell function. Some infants with no thymus have some T cells that presumably developed extrathymically; these T cells can reject a thymus graft. The purpose of this study is to design better immunosuppression use for complete DiGeorge anomaly subjects who have some T cells and different T cell function levels. This protocol includes 3 immunosuppression regimens to allow subjects with different T cell function levels to be suppressed adequately.. DiGeorge infants who have successful thymus transplants but remain with hypoparathyroidism must go to the clinic for frequent calcium levels and to the hospital for calcium infusions; these infants are at risk for seizures from low ...
T-cell receptor excision circle levels after allogeneic stem cell transplantation are predictive of relapse in patients with acute myeloid leukemia and myelodys
SPIRITUAL SIGNIFICANCE OF YOUR THYMUS GLAND / HEART CHAKRA - a lymphoid organ situated in the neck of vertebrates which produces T-lymphocytes for the immune system. The human thymus becomes much smaller at the approach of puberty.
Cell surface markers of mouse thymic dendritic cells have been studied by flow cytometry after isolation by collagenase digestion, separation of the low-density cell fraction and differential adherence. The dendritic cell preparation had a purity of , 90%, the contaminating population being essentially composed of thymocytes, macrophages constituting ,1%. Dendritic cells displayed high forward and low-intermediate side angle scatter, and expressed high levels of major histocompatibility complex (MHC) class I and class II molecules, the heat-stable antigen (HSA), the adhesion molecules Pgp-1 (CD44), LFA-1, ICAM-1 and low levels of Mac-1 and the leukocyte common antigen CD45. Thymic dendritic cells are negative for the stem cell antigen-2 (Sca-2), the B cell-specific form of CD45 (B220), the mouse macrophage markers Fc receptor and F4/80, and the granulocyte marker Gr-1. However, although they do not express the T cell markers Thy-1, CD2, CD3, CD4 and CD5, 20%-30% of dendritic cells are positive ...
Lecture (ca. 1907?) on the anatomy, physiology, diseases, and conditions of the thymus gland. The lecture is part of a set on the thorax and its component structures (see list at 2009.10.357). The lectures were part of the curriculum of the American School of Osteopathy in Kirksville, Missouri, and may have been compiled for a planned but unpublished book. The series author(s) drew heavily from standard medical textbooks of the era, to an extent that would be unacceptable today; possible source books that have been identified include James M. Anders, A Text-Book of the Practice of Medicine; Robley Dunglison, A Dictionary of Medical Science; Arthur R. Edwards, A Treatise on the Principles and Practice of Medicine; William Pepper, A Text-Book of the Theory and Practice of Medicine; and A.A. Stevens, A Manual of the Practice of Medicine. Such reliance on medical authors stands in stark contrast with the pains usually taken by early osteopathic writers to distance osteopathic practice from ...
Approach and Results-Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)-null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI+/+ mice, but no thymocyte apoptosis in SR-BI−/− mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI−/− mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI+/+ HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI−/− HDL had no such activity. Further study revealed that SR-BI+/+ HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI−/− HDL loses such regulatory activity. ...
TY - JOUR. T1 - The serum factor from patients with ulcerative colitis that induces T cell proliferation in the mouse thymus is interleukin-7. AU - Watanabe, Mamoru. AU - Watanabe, Noriaki. AU - Iwao, Yasushi. AU - Ogata, Haruhiko. AU - Kanai, Takanori. AU - Ueno, Yoshitaka. AU - Tsuchiya, Masaharu. AU - Ishii, Hiromasa. AU - Aiso, Sadakazu. AU - Habu, Sonoko. AU - Hibi, Toshifumi. PY - 1997/9/4. Y1 - 1997/9/4. N2 - The disturbance of immune regulatory T cells is related to the pathogenesis of ulcerative colitis. Here we demonstrated and characterized the serum factor from ulcerative colitis patients that induced proliferation of intrathymic T cells. The factor isolated from the patient sera by a combination of gel filtration and anion-exchange chromatography induced proliferation of CD4+CD8- intrathymic T cells in the organ-cultured embryonic mouse thymus. Purification and amino acid sequence analysis of the serum factor demonstrated that the N-terminal 12 sequence was homologous to that of ...
Background Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls. Results Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) ...
Deletion of the transcriptional modulator Cited2 in the mouse results in embryonic lethality, cardiovascular malformations, adrenal agenesis, cranial ganglia fusion, exencephaly, and left-right patterning defects, all seen with a varying degree of penetrance. The phenotypic heterogeneity, observed on different genetic backgrounds, indicates the existence of both genetic and environmental modifiers. Mice lacking the LIM domain-containing protein Lmo4 share specific phenotypes with Cited2 null embryos, such as embryonic lethality, cranial ganglia fusion, and exencephaly. These shared phenotypes suggested that Lmo4 may be a potential genetic modifier of the Cited2 phenotype. Examination of Lmo4-deficient embryos revealed partially penetrant cardiovascular malformations and hypoplastic thymus. Examination of Lmo4;Cited2 compound mutants indicated that there is a genetic interaction between Cited2 and Lmo4 in control of thymus development. Our data suggest that this may occur, in part, through control of
Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TCR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappa B, I kappa BNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains seven ankyrin repeats and is homologous to I kappa B family members. In class I and class II MHC-restricted TCR transgenic mice, transcription of I kappa BNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. I kappa BNS blocks transcription from NF-kappa B reporters, alters NF-kappa B electrophoretic mobility shifts, and interacts with NF-kappa B proteins in thymic nuclear lysates following TCR stimulation. Retroviral transduction of I kappa BNS in fetal thymic organ culture enhances TCR-triggered cell death consistent with its function in selection.. ...
Neural crest (NC)-derived mesenchyme has previously been shown to play an important role in the development of fetal thymus. Using Wnt1-Cre and Sox10-Cre mice crossed to Rosa26(eYfp) reporter mice, we have revealed NC-derived mesenchymal cells in the adult murine thymus. We report that NC-derived cells infiltrate the thymus before day 13.5 of embryonic development (E13.5) and differentiate into cells with characteristics of smooth muscle cells associated with large vessels, and pericytes associated with capillaries. In the adult organ at 3 mo of age, these NC-derived perivascular cells continue to be associated with the vasculature, providing structural support to the blood vessels and possibly regulating endothelial cell function.
During embryogenesis, the thymus and inferior parathyroid glands develop from the third pharyngeal pouch and migrate to their definite position. During this process, several anatomic variations may arise, with the thyroid being one of the most common sites of ectopic implantation for both organs. Here, we report the case of a young female patient, who underwent total thyroidectomy for papillary carcinoma of the thyroid. The patients history was remarkable for disorders of the genitourinary system. Histologic examination revealed the presence of well-differentiated intrathyroidal thymic tissue, containing an inferior parathyroid gland. While each individual entity has been well documented, this is one of the few reports in which concurrent presentation is reported. Given the fact that both the thymus and the inferior parathyroid are derivatives of the same embryonic structure (i.e. the third pharyngeal pouch), it is speculated that the present condition resulted from a failure in separation and ...
During embryogenesis, the thymus and inferior parathyroid glands develop from the third pharyngeal pouch and migrate to their definite position. During this process, several anatomic variations may arise, with the thyroid being one of the most common sites of ectopic implantation for both organs. Here, we report the case of a young female patient, who underwent total thyroidectomy for papillary carcinoma of the thyroid. The patients history was remarkable for disorders of the genitourinary system. Histologic examination revealed the presence of well-differentiated intrathyroidal thymic tissue, containing an inferior parathyroid gland. While each individual entity has been well documented, this is one of the few reports in which concurrent presentation is reported. Given the fact that both the thymus and the inferior parathyroid are derivatives of the same embryonic structure (i.e. the third pharyngeal pouch), it is speculated that the present condition resulted from a failure in separation and ...
The concentration of T-cell receptor rearrangement excision DNA circles (TRECs) in peripheral blood mononuclear cells (PBMCs) is currently known to be a marker of recent thymic emigrants. We evaluated the hypothesis that TREC values would be lower in childhood T-cell hematopoietic malignancies than …
The thymus is a complex cellular structure made up of several interdependent cell types and is the primary site for T cell development. A population of fetal thymic epithelial cells (TEC), marked by MTS20 and MTS24, when grafted in vivo can generate a functional thymus containing all thymic epithelial cells and is capab,e of supporting T cell differentiation. Further analysis using in vivo grafting experiments have determined the endoderm as the sole origin for all major thymic epithelial subsets. These findings suggest the possibility that a bipotent thmic epithelial progenitor cell (TEPC) gives rise to both cortical and medullary epithelial compartments. The first ai of this study was to address whether bipotent mouse TEPC give rise to both medullary and cortical epithelial cell populations and to begin to establish a model of TEC differentiation through ontogeny. Its second aim was to start to define condidtions for maintaining functionally undifferentiated RTEPC in vitro. Finally, as little ...
ATCC ® Normal Human Primary Renal Cortical Epithelial Cells, when grown in Renal Epithelial Cell Basal Media supplemented with Renal Epithelial Cell Growth Kit components, provide an ideal cell system to propagate renal epithelial cells in low serum (0.5% FBS) conditions. The cells are cryopreserved in the first passage to ensure the highest viability and plating efficiency. ATCC ® Primary Cell Solutions™ cells, media, supplements and reagents are quality tested together to guarantee optimum performance and reliability.
Myasthenia gravis is caused by a problem with the signals sent between the nerves and the muscles.. Its an autoimmune condition, which means its the result of the immune system (the bodys natural defence against infection) mistakenly attacking a healthy part of the body.. In myasthenia gravis, the immune system damages the communication system between the nerves and muscles, making the muscles weak and easily tired.. Its not clear why this happens, but its been linked to issues with the thymus gland (a gland in the chest thats part of the immune system).. Many people with myasthenia gravis have a thymus gland thats larger than normal. Around 1 in 10 people have an abnormal growth of the thymus called a thymoma. ...
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More than 50 years ago, Miller (107) conducted seminal studies on the immunological function of the thymus using neonatally thymectomized mice. The importance of this primary lymphoid organ was quickly established, as the thymus provides a unique microenvironment in which T cells or T lymphocytes undergo development, differentiation and clonal expansion during the physiological development of the immune system. In recent years, there has been a marked interest in the association between the immune system and the thymus, generating results that confirmed that the thymus was endowed with an immune function. The immune system has evolved to mount an effective defense against pathogens and to minimize deleterious immune-mediated inflammation caused by commensal microorganisms, immune responses against self and environmental antigens, and metabolic inflammatory disorders. It appears that Treg cell-mediated suppression serves as a vital mechanism in the negative regulation of immune-mediated ...
Results RCAN1-TG mice display T cell developmental defects in the thymus and peripheral immune tissues. Thymic cellularity is reduced by substantial losses of mature CD4 and CD8 thymocytes and medullary epithelium. In peripheral immune organs T lymphocytes are reduced in number and exhibit reduced proliferative capacity and aberrant cytokine production. These T cell defects are stem cell intrinsic in that transfer of wild type bone marrow into RCAN1-TG recipients restored medullary thymic epithelium and T cell numbers in the thymus, spleen and lymph nodes. However, bone marrow transplantation failed to improve T cell function, suggesting an additional role for RCAN1 in the non-haemopoietic compartment.. ...
Immunologic dysfunction was recently found to be one of the most important mechanisms underlying the initiation and development of atherosclerosis. Thymus involution can contribute to immune disturbance and disequilibrium of T-cell subsets. This study aimed to explore whether recent thymic emigration (RTE) is impaired in patients with coronary artery disease (CAD)....
TY - JOUR. T1 - INFLUENCE OF THE THYMUS ON ADRENOCORTICAL HYPERACTIVITY IN. AU - FACHET, J.. AU - VALLENT, K.. AU - Palkóvits, M.. AU - ACS, Z.. PY - 1964. Y1 - 1964. UR - http://www.scopus.com/inward/record.url?scp=78651150870&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=78651150870&partnerID=8YFLogxK. M3 - Article. C2 - 14239404. AN - SCOPUS:78651150870. VL - 20. SP - 281. EP - 287. JO - Acta Medica Academiae Scientiarum Hungaricae. JF - Acta Medica Academiae Scientiarum Hungaricae. SN - 0001-5989. ER - ...
The objective of this thesis was to investigate the effects of the somatotrope GH/IGF-1 axis upon the thymus. This work included two parts: 1. Translational research study: Thymus function in adult GH deficiency (AGHD) with and without GH treatment Background: Despite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse agerelated changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels. Methodology/Principal Findings: Twenty-two patients with documented AGHD were enrolled in ...
The thymus is a complex epithelial organ in which thymocyte development is dependent upon the sequential contribution of morphologically and phenotypically distinct stromal cell compartments. It is these microenvironments that provide the unique combination of cellular interactions, cytokines, and chemokines to induce thymocyte precursors to undergo a differentiation program that leads to the generation of functional T cells. Despite the indispensable role of thymic epithelium in the generation of T cells, the mediators of this process and the differentiation pathway undertaken by the primordial thymic epithelial cells are not well defined. There is a lack of lineage-specific cell-surface-associated markers, which are needed to characterize putative thymic epithelial stem cell populations. This review explores the role of thymic stromal cells in T-cell development and thymic organogenesis, as well as the molecular signals that contribute to the growth and expansion of primordial thymic epithelial cells.
Oleh : Nurjaman. Thymus gland is the important organ in immunity, especially in producing lymphocyte T cells. Prostaglandin is an antigenic substance that functions as a mitogen.. The aim of this to determine the influence of Prostaglandin as mitogen on the thymus gland of aged male rabbits and young male rabbits.. Forty male rabbits were divided into two groups, the firs group consists of twenty aged male rabbits and the second group consists of twenty young rabbits . The twenty aged rabbits were divided randomly into two groups (group I = 10 rabbits, group II = 10 rabbits). The twenty young rabbits were divided randomly into two groups (group I = 10 rabbits, group II = 10 rabbits). Before the experiment began, all rabbits were observed for one week for adaptation. After adaptation all rabbits were injected with prostaglandin intra musculary, 1.5 mg for each aged rabbit and 0.75 mg for each young rabbit. One week after injection all rabbits of group I (aged and young rabbits) were killed and ...
When your body is experiencing stress, it depletes stores of vitamins B and C quickly. Multivitamins, particularly stress formulas, include B vitamins in combination with vitamin C to assist the body with stress-coping mechanisms.. Vitamin B complex is necessary for anxiety and stress relief. These include vitamin B5, required by the thymus gland; B12, needed for the appropriate functioning of the nerve system; niacin for the production of serotonin that promotes a steady state of mind; and pantothenic acid for keeping stress hormones.. Vitamin C helps the adrenal glands react to stress by launching corticoids, which are hormones that trigger the battle or flight reaction. Scientists at the University of Alabama in Huntsville put lab rats under stress and discovered vitamin C decreased the levels of physical and psychological stress, including weight loss, enhancement of adrenal glands and size decrease of the thymus gland and the spleen.. ...
The Src-family and Syk/ZAP-70 family of protein tyrosine kinases (PTK) are required for T cell receptor (TCR) functions. We provide evidence that the Src-family PTK Lck is responsible for regulating the constitutive tyrosine phosphorylation of the TCR zeta subunit in murine thymocytes. Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient mice largely failed to induce the phosphorylation of TCR-zeta, CD3 epsilon, or ZAP-70. In contrast, we find that the TCR-zeta subunit is weakly constitutively tyrosine phosphorylated in peripheral T cells isolated from Lck-null mice. These data suggest that Lck has a functional role in regulation of TCR signal transduction in thymocytes. In peripheral T cells, other Src-family PTKs such as Fyn may partially compensate for the absence of Lck. ...
Signaling through the Notch1 receptor is essential for T cell development in the thymus. Stromal OP9 cells ectopically expressing the Notch ligand Delta-like1 mimic the thymic environment by inducing hemopoietic stem cells to undergo in vitro T cell development. Notch1 is also expressed on Pax5-/- pro-B cells, which are clonable lymphoid progenitors with a latent myeloid potential. In this study, we demonstrate that Pax5-/- progenitors efficiently differentiate in vitro into CD4+CD8+ alphabeta and gammadelta T cells upon coculture with OP9-Delta-like1 cells. In vitro T cell development of Pax5-/- progenitors strictly depends on Notch1 function and progresses through normal developmental stages by expressing T cell markers and rearranging TCRbeta, gamma, and delta loci in the correct temporal sequence. Notch-stimulated Pax5-/- progenitors efficiently down-regulate the expression of B cell-specific genes, consistent with a role of Notch1 in preventing B lymphopoiesis in the thymus. At the same ...
Hypergravity provokes a temporary reduction in CD4+CD8+thymocyte number and a persistent decrease in medullary thymic epithelial cell frequency in mice ...
Project ReportCharacterization of micro RNAs (mir 146a, 10a and 34a) involved in the thymic epithelial cell development Autoimmune diseases occur when the body...
T cells, like all other white blood cells involved in innate and adaptive immunity, are formed from multipotent hematopoietic stem cells (HSCs) in the bone marrow (see [link]). However, unlike the white blood cells of innate immunity, eventual T cells differentiate first into lymphoid stem cells that then become small, immature lymphocytes, sometimes called lymphoblasts. The first steps of differentiation occur in the red marrow of bones ([link]), after which immature T lymphocytes enter the bloodstream and travel to the thymus for the final steps of maturation ([link]). Once in the thymus, the immature T lymphocytes are referred to as thymocytes.. The maturation of thymocytes within the thymus can be divided into tree critical steps of positive and negative selection, collectively referred to as thymic selection. The first step of thymic selection occurs in the cortex of the thymus and involves the development of a functional T-cell receptor (TCR) that is required for activation by APCs. ...
Mammalian ontogenesis and postnatal histogenesis involves the dynamic and appropriate interaction of two growth related phenomena: progression and regression. The thymus gland is the organ of the mammalian body that exhibits the most profound involution during normal postnatal histogenesis. Involution of the thymus can be compared to similarly regressive processes during the ontogeny of holometabolic insects, as well as to the spontaneous regression of neoplasms. It can be expected that in the future a better understanding of neoplastic regression will result from the comparison of ontogenetic processes from taxonomically far-removed regressive processes, and the evaluation of various factors that promote progression and regression ...
TY - JOUR. T1 - The selection of lymphocytes in the thymus. AU - Fabbi, M.. PY - 1995. Y1 - 1995. N2 - The thymus is the main site of T cell maturation. Upon seeding, thymus T cell precursors undergo a complex series of maturational events that involve antigen receptor gene assembly by somatic recombination of gene segments. This process is largely stochastic, therefore a mechanism must exist to shape this antigen receptor repertoire in order to achieve both self restriction (defined as the capacity of a T cell to recognise a peptide antigen in the context of self major histocompatibility complex molecules and self tolerance. This outcome is ensured via selection processes that promote the expansion of those thymocytes that see antigen(s) only in the context of self major histocompatibility gene products. In contrast, those cells that do not fulfill these recognition requirements or that recognise auto antigens with high affinity are deleted. This review will focus on the development of the ...
Abstract Thymocyte development is tightly regulated, requiring successful transit of cells through several developmental stages and checkpoints prior to thymic egress. Each checkpoint of thymocyte development, involves induction or repression of a particular set of genes. Disruptions in gene regulation leads to developmental arrest, a failure to generate T cells and deficits in adaptive immunity. Gene expression is coordinated by transcriptional activators, repressors, and chromatin modifiers. In general, histone acetylation promotes gene expression while histone deacetylation leads to repression. We investigated the role of histone deacetylase-3 (HDAC3) in T cell development using CD2-icre conditional knockout (HDAC3- cKO) mice. Although T cells co-express several HDAC family members during development, these other HDAC family members cannot compensate for the loss of HDAC3 as HDAC3-cKO mice have a block in T cell development at the DP stage due to an inability to undergo positive selection. ...
TY - JOUR. T1 - Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins. AU - Huang, Fang. AU - Kitaura, Yasuyuki. AU - Jang, Ihn Kyung. AU - Naramura, Mayumi. AU - Kole, Hemanta H H.. AU - Liu, Liping. AU - Qin, Haiyan. AU - Schlissel, Mark S S.. AU - Gu, Hua. PY - 2006/10. Y1 - 2006/10. N2 - Casitas B cell lymphoma (Cbl) proteins are negative regulators for T cell antigen receptor (TCR) signaling. Their role in thymocyte development remains unclear. Here we show that simultaneous inactivation of c-Cbl and Cbl-b in thymocytes enhanced thymic negative selection and altered the ratio of CD4+ and CD8+ T cells. Strikingly, the mutant thymocytes developed into CD4+- and CD8+-lineage T cells independent of the major histocompatibility complex (MHC), indicating that the CD4+- and CD8+-lineage development programs are constitutively active in the absence of c-Cbl and Cbl-b. The mutant double-positive (DP) thymocytes exhibited ...
This 5 year competing application describes an opportunity to explore the long term outcomes of thymus transplantation in detail, with particular focus on the r...
in Journal of the National Cancer Institute (1996), 88(12), 824-31. BACKGROUND: Split-dose irradiation (1.75 Gy given weekly for 4 weeks) of C57BL/Ka mice induces the emergence of preleukemic cells (PLCs). These cells develop into leukemic cells after a latency period of ... [more ▼]. BACKGROUND: Split-dose irradiation (1.75 Gy given weekly for 4 weeks) of C57BL/Ka mice induces the emergence of preleukemic cells (PLCs). These cells develop into leukemic cells after a latency period of 3-6 months. The survival and transformation of PLCs are dependent on radiation-induced alterations of the thymic epithelium and of resident lymphocyte (i.e., thymocyte) subpopulations in the thymus. PLCs can be eliminated, concomitantly with the restoration of the thymus, by grafting bone marrow cells immediately after the last irradiation. Our hypothesis was that any agent able to restore the thymus after leukemogenic irradiation would exert the same effects as a bone marrow graft. Tumor necrosis factor-alpha ...
Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal i …