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Inhibition by chlorpromazine of lymphokine-specific mRNA expression in human thymocytes.

This study was designed to determine the effect of the phenothiazine chlorpromazine (CPZ) on the activation of human thymocytes. We provide evidence that CPZ inhibits the accumulation of mRNA specific for the lymphokines, interleukin 2, interferon-gamma, tumor necrosis factor alpha and the proto-oncogene c-myc; by contrast, the accumulation of mRNA specific for the alpha chain of the interleukin 2 receptor and the subsequent early expression of Tac antigen on the cell surface is not inhibited by CPZ. The inhibition of the expression of lymphokine-specific mRNA results in a decrease in interfer…

Formation of adenosine 3',5'-monophosphate from adenosine in mouse thymocytes.

The effect of adenosine on the mouse thymocyte adenylate cyclase-adenosine 3':5'-monophosphate (cyclic AMP) system was examined. Adenosine, … denosine analogues tested, only 2-chloro- and 2-fluoroadenosine significantly increased cyclic AMP. Thymocytes prelabeled with [14C]adenine exhibited dramatic increases in cyclic [14C]AMP 10 min after addition of adenosine or prostaglandin E1 which corresponded to simultaneously determined increases in total cyclic AMP. Using [14C]adenosine, the percent of t …

Protective role of vitamin C in diazepam-induced apoptosis in rat thymocytes.

Diazepam, a peripheral-type benzodiazepine receptor ligand, is widely used as a therapeutic agent. On the other hand, peripheral-type benzodiazepines have been shown to induce apoptosis in different immune cell types. In this study, we examined the possible protective role of vitamin C in diazepam-induced apoptosis and evaluated the cellular content of glutathione during this process. Rat thymocytes were incubated for 24 hours with diazepam and increasing concentrations of vitamin C or with diazepam alone. The exposure to diazepam resulted in an increase in apoptotic cell death and decrease in…

Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes.

T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both…

NF-kappaB activation in premalignant mouse tal-1/scl thymocytes and tumors.

TAL-1/SCL activation is a common genetic event in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Expression of tal-1/scl or a DNA binding mutant of tal-1/scl induces arrest of thymocyte development, resulting in decreases in double-positive and single-positive CD4 thymocytes. Moreover, nuclear p65/p50 heterodimers are detected in premalignant tal-1/scl and mut tal-1/scl thymocytes, suggesting that E2A depletion may induce developmental arrest and stimulate NF-kappaB activation. Increased NF-kappaB activity is also observed in tal-1/scl tumors and bcl-2 is overexpressed. To examine the …

Unresponsiveness of CD4-8+/- thymocytes to lectin stimulation in LEC mutant rats.

A mutant strain of rat, LEC, shows a novel arrest of T-cell maturation from CD4+8+ to CD4+8-, but not to CD4-8+ cells in the thymus. The responsible mutant locus is designated the thid, which was acted upon in a recessive manner of inheritance. We found that LEC rat thymocytes failed to respond to interleukin (IL)-1, IL-6 and IL-7 in the presence of the mitogenic lectins, Allo A or concanavalin A (Con A). The unresponsiveness appeared to be due to unresponsiveness to the lectin stimulation rather than because of cytokine stimulation. Normal rat CD4-8+/- (consisting of CD4-8+ and CD4-8- thymocy…

Effects of forskolin and triiodothyronine on cyclic AMP production in rat thymocytes.

The effects of forskolin, 3,5,3'-L-triiodothyronine, and isobutyl methylxanthine on the accumulation of cyclic AMP were studied in rat thymocytes in vitro. Forskolin was found to stimulate markedly the production of intracellular cAMP which was partially released from the cells into the medium. Isobutyl methylxanthine, an inhibitor of cAMP phosphodiesterase, markedly potentiated the effect of forskolin on intracellular cAMP concentration, while triiodothyronine was ineffective. However, triiodothyronine acted synergically with forskolin and/or isobutyl methylxanthine. It was confirmed that low…

Умножение лимфоцита в тимоцитах во время его стойкости в мышах.

Стойкость вируса лимфоцита (LCM) у мышей, инфицированных утечкой или неонатальным заболеванием, обусловлена повреждением конкретных подмножеств лимфоцитов, зависящих от тимуса, которые во взрослой обычной мыши участвуют в ликвидации вируса ЛХМ. Вирусно-тимоцитные взаимодействия были изучены, так как вероятно, что это повреждение происходит в тимусе. Используя анализ инфекционного центра, мы обнаружили, что около 1% тимоцитов мышей плода и неонатальных мышей были продуктивно заражены вирусом, в то время как тимоциты от мышей более старшего возраста были отвращены к инфекции. Зараженные клетки б

Совпадение в аннотации оригинала
Persistence of lymphocytic choriomeningitis (LCM) virus in mice infected in utero or neonatally is due to impairment of the specific subsets … pairment takes place in the thymus. Using an infectious centre assay, we found that about 1% of the thymocytes from foetal and neonatal mice were productively infected by the virus while thymocytes from older mice were refractory to infection. The infected cells were Thy 1-positive and agglutinated by peanut lectin together with immature lymphocytes. Later, …

Sequential analysis of the thymocyte differentiation in fully allogeneic bone marrow chimera in mice. I. Relationship between functions and surface characteristics of thymocytes.

Differentiation of thymocytes according to surface phenotype, functional status and cell size was investigated using fully allogeneic bone marrow chimeras. Most of the donor-derived thymocytes obtained from chimeras 9 days after hematopoietic reconstitution were CD4-8- and IL2R+. At day 14, CD4+8+ cells became prominent in the thymus. Eighty-six per cent of thymocytes were CD4+8+ and 9% were CD4-8- at this stage. After day 21, the proportion of CD4+8- or CD4-8+ single positive cells transiently increased and then declined to normal level at day 42. Further, the mean size of CD4+ or CD8+ single…

Development in vitro of human CD4+ thymocytes into functionally mature Th2 cells. Exogenous interleukin-12 is required for priming thymocytes to produce both Th1 cytokines and interleukin-10.

Fresh postnatal thymocyte cell suspensions were directly cloned under limiting dilution conditions with either phytohemagglutinin or toxic s … cell clones generated from peripheral blood, virtually all CD4+ T cell clones generated from human thymocytes produced high concentrations of IL-2, IL-4 and IL-5, but no IFN-gamma, TNF-beta or IL-10. Moreover, after activation, these clones expressed on their surface membrane both CD30 and CD40 ligand, but not the product of lymphocyte activation gene (LAG) …

Effects of sex steroids on thymic epithelium and thymocyte development.

Sex steroid hormones have major effects on the thymus. Age-related increases in androgens and estrogens and pregnancy-induced increases in p … ts of steroids on TEC, especially thymic involution, the direct effects of sex steroid signaling in thymocytes are less well understood. We outline studies that could be important in addressing these possibilities, and highlight suggestive findings of sex steroid generation within the thymus itself.

Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness.

Generation of a self-tolerant but antigen-responsive T cell repertoire occurs in the thymus. Although glucocorticoids are usually considered immunosuppressive, there is also evidence that they play a positive role in thymocyte selection. To address the question of how endogenous glucocorticoids might influence the adaptive immune response, we generated GRlck-Cre mice, in which the glucocorticoid receptor gene (GR) is deleted in thymocytes prior to selection. These mice were immunocompromised, with reduced polyclonal T cell proliferative responses to alloantigen, defined peptide antigens, and v…

Functional glycosylation of dystroglycan is crucial for thymocyte development in the mouse.

BACKGROUND: Alpha-dystroglycan (alpha-DG) is a cell surface receptor providing a molecular link between the extracellular matrix (ECM) and the actin-based cytoskeleton. During its biosynthesis, alpha-DG undergoes specific and unusual O-glycosylation crucial for its function as a high-affinity cellular receptor for ECM proteins. METHODOLOGY/PRINCIPAL FINDINGS: We report that expression of functionally glycosylated alpha-DG during thymic development is tightly regulated in developing T cells and largely confined to CD4(-)CD8(-) double negative (DN) thymocytes. Ablation of DG in T cells had no e…

The role of mitochondria in nitric oxide-mediated thymocyte apoptosis.

The aim of this study was to analyze whether immunosuppressants could affect NO-induced thymocytes apoptosis. S-Nitroso-N-acetyl-D,L-penicillamine (SNAP, an NO donor) has an apoptotic effect on murine thymocytes. This NO-induced thymocyte apoptosis is associated with a reduced uptake of DiOC(6), a fluorochrome which incorporates into cells depending on their mitochondrial membrane potential (DeltaPsi(m)). The immunosuppressant, cyclosporin A, partially inhibited NO-induced thymocyte apoptosis as well as the reduction of DeltaPsi(m). In contrast, another immunosuppressant, FK506, did not affect…

Sex hormones and the thymus in relation to thymocyte proliferation and maturation.

This paper reviews the mechanism of sex hormone actions on the thymus, presenting mainly our data obtained at the cellular and molecular levels. First, data supporting the "genomic" action via the nuclear sex hormone receptor complexes are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co-localized in thymic epithelial cells, but not in T cells; 2) production/expression of thymic factors (thymulin, thymosin alpha 1) are remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T cell subpopulations in the thymus; and 4) sex hormones strongly inf

Involvement of CXCL12/CXCR4 pair in migration of thymocytes from lactating mice.

During the postpartum and lactation period, the involuted thymus, affected by pregnancy hormones, initiates its morphophysiological recovery with the positive regulation of the hormone prolactin (PRL), present at high levels during lactation. PRL has pleiotropic effects on thymic epithelial cells, thymocytes, as well as on elements of the extracellular matrix. In this study, we evaluated the production of the chemokine CXCL12 by the thymic microenvironment and its receptor, CXCR4, by thymocytes from lactating female mice. To achieve this objective, we used C57BL/6 female mice that were nullipa…

Disruption of Notch signaling by KGF induces a developmental pause in thymocytes.

Keratinocyte growth factor (KGF) has been proposed as a therapeutic adjuvant to enhance T cell immune reconstitution, particularly following stem cell transplantation. Here, we demonstrate that the long-term KGF-induced increase in thymic cellularity and thymocyte differentiation is preceded by a transient developmental block prior to the β-selection checkpoint, observed as early as day 2 following KGF treatment. This early block is characterized by an increased expansion of uncommitted thymocytes and is driven by KGF-induced alterations in both cortical and medullary thymic epithelial cells (…

Cryopreservation of mouse thymus depletes thymocytes but supports immune reconstitution on transplantation.

Cryopreservation of mouse thymus depletes donor thymocytes but preserves thymus function when transplanted after thawing into athymic mice. No differences in immune reconstitution were observed between fresh and frozen/thawed transplants suggesting that donor thymocyte depletion does not affect outcome. Thus, cryopreservation of thymus may improve outcomes in thymus transplant patients.

Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages.

Interactions of developing T cells with Aire+ medullary thymic epithelial cells expressing high levels of MHCII molecules (mTEChi) are critical for the induction of central tolerance in the thymus. In turn, thymocytes regulate the cellularity of Aire+ mTEChi. However, it remains unknown whether thymocytes control the precursors of Aire+ mTEChi that are contained in mTEClo cells or other mTEClo subsets that have recently been delineated by single-cell transcriptomic analyses. Here, using three distinct transgenic mouse models, in which antigen presentation between mTECs and CD4+ thymocytes is p…