Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die. Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with ...

We have previously shown that polyamine levels rapidly decrease in thymocytes undergoing apoptosis, and that ornithine decarboxylase increases early but too transiently to maintain elevated polyamine levels. These data led us to suppose that a precocious ornithine decarboxylase degradation might be responsible for the imbalance of polyamine metabolism. Ornithine decarboxylase ...

Apoptosis is a well defined physiological process characterised by many specific features including DNA fragmentation and protease activation. Cell membrane-associated changes such as the altered exposure of phosphatidylserine and glycosylation patterns have also been described. We investigate here the change in exposure of surface alpha-L-fucose residues during thymocyte and P815 ...

Newborn mice infected with ts1, a mutant of the Moloney murine leukemia virus, develop neuroimmunodegeneration with death and damage of thymocytes, astrocytes, and motor neurons by 24-38 days. T cells, B cells, and astrocytes, but not neurons, are infected by the virus. Primary splenocytes and thymocytes isolated from age-matched infected ...

INTRODUCTION: Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which preleukemic cells progressively transform into leukemic cells within an abnormal thymic microenvironment. A bone marrow graft or repeated cytokine injections prevent lymphoma development. We think that these treatments restore altered mechanisms controlling apoptosis. ...

A family of caspases has been implicated as an effector in various forms of apoptosis. The present study investigated whether this family of proteases is involved in the induction of intrathymic clonal deletion in comparison with apoptosis induced in the thymus by various signals. Potent apoptosis of thymocytes was induced ...

Fas, a cell surface receptor, can induce apoptosis after cross-linking with its ligand. Fewer than 3% of human thymocytes strongly express Fas. We report that Fas antigen expression can be upregulated by two signaling pathways in vitro, one mediated by anti-CD3 and the other by interleukin-7 + interferon-gamma. The two ...

We reported previously that thymic lymphomas from mice expressing transgenic TCR autoreactive against male (HY) antigen were resistant to anti-CD3 antibody-mediated induction of apoptosis although they were responding to TCR triggering. To test whether thymic lymphomas were specifically resistant to TCR-dependent Ca(++)-mediated induction of apoptosis, we have measured apoptosis of ...

Irradiation with gamma rays induces apoptosis of thymocytes by a p53-dependent pathway, but its mechanism is not clear. In this study, we report that gamma-ray-induced apoptosis was associated with the intracellular alkalinization of the thymocytes. After exposure to gamma rays, thymocytes underwent apoptosis when cultured in vitro, and the degree ...

CD99 is a cell surface molecule involved in the aggregation of lymphocytes and apoptosis of immature cortical thymocytes. Despite its high level expression on immature cortical thymocytes, the functional roles of this molecule during thymic selection are only now being elucidated. Examination of the effects of CD99 engagement on the ...

Inducible serum proteins whose concentrations oscillate between nontolerogenic and tolerogenic levels pose a particular challenge to the maintenance of self-tolerance. Temporal restrictions of intrathymic antigen supply should prevent continuous central tolerization of T cells, in analogy to the spatial limitation imposed by tissue-restricted antigen expression. Major acute-phase proteins such as ...

During Anuran metamorphosis larval structures regress, adult structures form anew and impaired T cell immune functions are noted, as are alterations in endogenous glucocorticoid titers. In situ histological data, after staining for DNA fragmentation, reveal patterns of lymphocyte suicide in the thymus and spleen of non-antigenically challenged, laboratory bred, developing ...

The mechanisms by which immature thymocyte apoptosis is induced during negative selection are poorly defined. Reports demonstrated that cross-linking of T-cell receptor leads to stromal cell activation, expression of inducible nitric oxide synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined, whether NO directly or indirectly, through peroxynitrite formation, ...

Increasing evidence suggests that some members of the neurotrophic factor family of neurotrophins could be implicated in the regulation of immune responses. Neurotrophins, as well as their tyrosine kinase signal-transducing receptors (the so-called Trk neurotrophin receptors), have been detected in different lymphoid tissues, although their cellular localization is not well ...

T-cell negative selection, a process by which intrathymic immunological tolerance is induced, involves the apoptosis-mediated clonal deletion of potentially autoreactive T cells. Although different experimental approaches suggest that this process is triggered as the result of activation-mediated cell death, the signal transduction pathways underlying this process is not fully understood. ...

Thymocytes undergo a complex process of differentiation, largely dependent on interactions with the thymic microenvironment, a tridimensional cellular network formed by epithelial cells, macrophages, dendritic cells, and fibroblasts. One key cellular interaction involves the TCR-CD3 complex expressed by thymocytes with MHC-peptide complexes present on microenvironmental cells. Additionally, thymic epithelial cells ...

OBJECTIVE: Glucocorticoids (GCs) are the drugs of first choice for treatment of systemic lupus erythematosus (SLE). However, the disease in some patients is resistant to these agents. This study evaluated the possibility of a relationship between response to GC treatment and the rate of apoptosis in vitro, and also analyzed ...

The critical role of the thymus in the development of the immune system was unknown until recently. For a long time physicians were puzzled by the presence of a large thymus in early life and attributed many symptoms to it. This review briefly covers the history of the thymus and ...

T cells undergo rigorous selection processes in the thymus that are necessary to prevent T cells with either autoreactive or nonfunctional T-cell receptors (TCRs) from entering the periphery. Although both positive and negative selection depend on TCR-mediated signals, the means by which a thymocyte interprets these signals to result in ...

Apoptosis represents the main mechanism involved in the intrathymic cell selection. The involution and atrophy of the thymic gland during aging has been associated with an altered representation of thymocyte subsets and particularly of CD4+CD8+ double-positive (DP) thymocytes, i.e., the cell population mainly involved in thymocyte selection. The aim of ...

Glucocorticoids are well known to stimulate apoptosis in immature thymocytes. Apoptosis in this and other cells is characterized by cell shrinkage, DNA fragmentation and activation of a class of proteases named caspases. We have utilized the flow cytometer to evaluate the coordinate regulation of cell shrinkage and DNA fragmentation in ...

We previously demonstrated that infection of primary human thymic dendritic cells (DCs) with laboratory strains of HIV leads to the release of soluble factor(s) which induced thymocyte killing. In the present paper, we extend the characterization of this process. Our results reveal that primary HIV-1 isolates are similarly able to ...

Mechanisms of androgen-induced thymic involution are largely undefined. We have found that significant decreases in thymic size occur 2-4 h after a dose of testosterone is administered to castrated male mice. This rapid rate of change suggests a role for androgen-induced apoptosis in modulating the size and composition of the ...

Carbon monoxide (CO) induces acute or chronic toxicity, according to the level and duration of the exposure. Since chronic CO exposure was shown to have immunosuppressive effects (as it decreases the frequency of rat splenic immunocompetent cells and immunoglobulin production), we investigated the effect of CO on thymocytes, since these ...

The role of growth hormone (GH) in modulating the adult immune response is receiving increased attention; however, its role in the development of immune competence in the fetus has not been defined. In order to begin to address the role of GH in the ontogeny of the immune response. cells ...

BACKGROUND: The thymus plays important roles in host defense, which may be impaired after burn injury. The effects of thermal injury on thymocytes were investigated in male Wistar rats. METHODS: Changes in thymus weight and content of glutathione and corticosterone were determined after burn injury. Apoptosis of thymocytes was detected ...

To evaluate the role of B7 on thymocyte activation and apoptosis, we took advantage of TCR transgenic mice in which the majority of thymocytes express a uniform TCR that is specific for ovalbumin. We also prepared Chinese hamster ovary (CHO) cells expressing B7 and appropriate class II molecules. We found ...

To address the effect of extremely low frequency electromagnetic fields on programmed cell death we assessed both the spontaneous and dexamethasone (Dex)-induced apoptosis of thymocytes and spleen cells from mice submitted to a long-term continuous exposure of a 0.4-1.0 microT 60 Hz magnetic field or an 8-20 microT direct current ...

In vitro interactions of thymocytes and thymocyte hybridomas with cortical (R-TNC.1) and medullary (TE-R 2.5) rat thymic epithelial-cell (TEC) lines were studied. It was found that the cortical line had better adhesion capability. It bound exclusively immature CD4+ CD8+ alpha beta TCRlo thymocytes, induced apoptosis of a subset of these ...

For several years, our group has been studying the in vivo role of adrenergic and cholinergic mechanisms in the immune-neuroendocrine dialogue in the rat model. The main results of these studies can be summarized as follows: (1) exogenous or endogenous catecholamines suppress PBL functions through alpha-2-receptor-mediated mechanisms, lymphocytes of the ...

The topical glucocorticoids (GCs) represent the treatment of choice for many types of inflammatory dermatoses. Despite the extensive use of this class of drugs as first line therapy the mechanism of their action is uncertain. It is clear that the multiplicity of actions of the topical GCs is an important ...

BACKGROUND: Aging in humans has been associated with the progressive loss of renal mass. This has been considered to account for a significant reduction of glomerular filtration rate in the aging population. In addition, aging is associated with a compromised immune system. Macrophages, thymocytes, and splenocytes play an important role ...

BACKGROUND: FK506 and glucocorticoids are used for allograft rejection, graft-versus-host disease, and autoimmune diseases. MATERIALS: We investigated the combined effect of FK506 and glucocorticoids on T-cell apoptosis. RESULTS: Dexamethasone injection in mice reduced the number of CD4+CD8+ thymocytes by increasing DNA fragmentation. Pretreatment with FK506 significantly augmented thymocyte DNA fragmentation ...

Cysteine proteases of the CED-3 and ICE family have been recently proposed as the ultimate executioners in several mammalian cell death pathways. Among them, the cysteine protease CPP32 has been shown to participate in programmed cell death (PCD), or apoptosis, affecting lymphoid cells in vitro. In the thymus, negative selection ...

We have shown that an antibody (9C10) to the alpha 4 integrin induces apoptosis in murine immature CD4+ CD8+ thymocytes and in activated (but not resting) mature lymph node T cells. In both cases, apoptosis is blocked by the highly selective protein kinase C (PKC) inhibitor Ro31.8425, suggesting that 9C10 ...

Linomide, a quinoline-3-carboxamide, has a pleiotropic immune modulating capacity and inhibits development as well as progression of disease in animal models of autoimmunity. Linomide treatment of mice resulted in a dramatic, dose-dependent decrease of the thymic cell number shortly after the start of administration. Flow cytometric analysis revealed that the ...

Curcumin (diferuoylmethane), the yellow pigment in the rhizome of tumeric (Curcuma longa), an ingredient of curry spice, is known to exhibit a variety of pharmacological effects including antitumor, antiinflammatory, and antiinfectious activities. Although its precise mode of action remains elusive, curcumin has been shown to suppress the activity of the ...

Despite the importance of glucocorticoids (GCs) to modern medicine, the physiological role of endogenous corticosteroids in immunomodulation is poorly understood. This article discusses evidence suggesting that endogenous GCs not only suppress but also direct and enhance immune functions. These often overlooked actions might well be more important than the inhibitory ...

The fate of different nuclear ribonucleoprotein (RNP) components was investigated during spontaneous apoptosis of thymocytes using specific monoclonal antibodies against snRNPs, hnRNPs, and ribosomal proteins at light and electron microscopy levels and by flow cytometry. It was found that, during apoptosis, nuclear RNP-containing structures (perichromatin granules, interchromatin granules, and perichromatin ...

Proper development of the thymus is critical for an individual to acquire full immune capability. A full complement of the components that participate in thymic development, interacting with each other at the correct time, is required for maturation. In order to establish the microenvironment necessary for T-cell differentiation, the epithelial ...

Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent ...

Ethylene dimethanesulphonate (EDS) is an alkylating agent which is widely assumed to specifically kill Leydig cells leaving other biological systems intact. However, after EDS treatment of the male rat the thymus reversibly involutes and the gonadal regional lymph nodes are activated. In the present experiments we have demonstrated that EDS ...

Metamorphosis in the South African clawed frog, Xenopus laevis, results in significant changes in the immune system. It is characterized by a striking involution of the thymus and spleen followed by lymphocyte expansion in the postmetamorphic period. While thyroid hormones are generally thought to be the most important mediators of ...

The adoptive transfer of auto-reactive T cells specific for S100 beta protein mediates experimental autoimmune panencephalomyelitis, an inflammatory autoimmune disease of the nervous system and eye. However, unlike classical encephalitogenic autoantigens which are components of the myelin membrane and restricted to the nervous system, S100 beta is expressed by many ...

Both methylprednisolone (MPS) and 2-chloroadenosine (2-CA) were shown previously to induce DNA fragmentation and cell death in human thymocytes at an optimum concentration of 1 and 40 microM, respectively. Though both compounds affected the CD4+CD8+ population, 2-CA depleted primarily thymocytes expressing medium or high levels of CD3-T-cell receptor molecule, while ...

In the present study the susceptibility of different subsets of immature rat thymocytes to undergo apoptosis was examined. Unfractionated rat thymocytes were negatively enriched into immature double positive (CD4+ CD8+), immature single positive (CD4- CD8+ CD3-) and triple negative (CD4- CD8- CD3-) thymocytes. These enriched subsets of immature thymocytes were ...

Galectin-1, a beta-galactoside binding protein, is produced by thymic epithelial cells and binds to human thymocytes. We have previously reported that galectin-1 induces the apoptosis of activated T lymphocytes. Because the majority of thymocytes die via apoptosis while still within the thymus, we tested whether galectin-1 could induce the apoptosis ...

To find anti-apoptotic substances in plant resources, a microassay method for estimating DNA fragmentation was established using fluorochrome 3,5-diaminobenzoic acid dihydrochloride. Examination was made of various herbal medicines for inhibitory effects on glucocorticoid-induced apoptosis in thymocytes. Several Kampo medicines, e.g. Oren-gedoku-to and San'o-shashin-to, were found to inhibit dexamethasone-induced apoptosis in ...

To elucidate the mechanism of apoptosis in matured T cells, we examined the effect of phorbol esters capable of activating protein kinase C, cAMP agonists, calcium ionophores, and dexamethasone on apoptosis in mouse splenic T cells. All of these agents induced apoptosis in thymocytes. Neither phorbol esters nor calcium ionophores ...

The transcription factor Nur77 (NGFI-B), a member of the steroid nuclear receptor superfamily, is induced to a high level during T-cell receptor (TCR)-mediated apoptosis. A transgenic dominant-negative Nur77 protein can inhibit the apoptotic process accompanying negative selection in thymocytes, while constitutive expression of Nur77 leads to massive cell death. Nur77-deficient ...