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PubMed1989

Emigration of B cells from chicken bursa of Fabricius.

The extent of emigration of cells from the bursa of Fabricius to the periphery was estimated. Per anum application of fluorescein isothiocyanate to label bursal cells in situ was used. Migrant cells can be visualized on frozen sections or cell suspensions of peripheral organs by their fluorescence. The data show that at 2-3 weeks after hatching about 5% of bursal cells leave the bursa per day. Since the bursal cells divide rapidly, this indicates that the vast majority (95%) of bursal cells die in situ. Cells that leave the bursa are surface IgM positive and go first to peripheral blood and later into B cell areas of spleen, thymus and cecal tonsils. The results are also discussed on the basis of their implication for the generation of antibody diversity in the chicken bursa.

Animals↗
PubMed1990

Differential peripheral expansion and in vivo antigen reactivity of alpha/beta and gamma/delta T cells emigrating from the early fetal lamb thymus.

The concentrations of different lymphocyte subsets in the blood of lambs which had been thymectomized (Tx) in utero between days 67-75 of fetal gestation were measured at birth and at various intervals during the first year of life. Compared to thymus-intact (Ti) controls, Tx lambs were severely depleted of both alpha/beta and gamma/delta T cells at birth (less than 10% of control levels). The majority of the residual alpha/beta T cells present in Tx lambs at birth were CD4+CD8-. As the Tx lambs aged, the concentration of alpha/beta T cells in blood increased steadily to reach levels around 50% of control values. In contrast, the circulating gamma/delta T cells did not expand in Tx animals and remained barely detectable throughout the observation period, although these cells accounted for 30%-60% of the T cells in the blood of Ti lambs. The expansion of alpha/beta but not gamma/delta T cells was also reflected in changes in the cellular composition of solid lymphoid organs in Tx lambs. B cell numbers were similar in both groups at birth but Tx lambs were persistently B lymphopenic from 3 weeks of age onwards. The alpha/beta T cells that had expanded in Tx lambs responded to stimulation with bacterial antigens in a way that was qualitatively similar to the response in Ti lambs. By contrast, the few gamma/delta T cells in Tx lambs responded abnormally. Our results show that although sheep alpha/beta and gamma/delta T cells are equally thymus dependent during ontogeny, the early fetal thymic emigrants which establish the two T cell lineages in the periphery have strikingly different antigen reactivities and capacities for self-renewal and expansion.

Aging↗
PubMed1991

A pertussis toxin-sensitive process controls thymocyte emigration.

Although it is well known that essentially all peripheral T cells are derived from bone marrow progenitors that mature in the thymus, the mechanism whereby thymocytes gain access to peripheral compartments is obscure. We have learned that this process is sensitive to pertussis toxin (PT). Transgenic lck-PT mice were generated which express the catalytic subunit of PT in all thymocytes. In a previous study we observed that T cell receptor signaling is unimpaired in these cells despite the virtual elimination of their Gi protein signal transduction elements through endogenous PT activity. Here we demonstrate that mature T lineage cells accumulate in lck-PT thymuses and fail to populate peripheral lymphoid organs. The accumulating cells closely resemble normal peripheral T lymphocytes with respect to cell surface phenotype and responses to allogeneic spleen cells, yet perform poorly in in vivo homing assays. This migratory defect does not result from deficient expression of common homing receptors or alterations in intracellular cAMP concentrations. Based on these results, we propose that a novel PT-sensitive signaling pathway, almost certainly involving a Gi protein, is required for thymocyte emigration.

Animals↗
PubMed1992

Functional maturation of recent thymic emigrants in the periphery: development of alloreactivity correlates with the cyclic expression of CD45RC isoforms.

The transition from fully developed CD4+CD8- single-positive (SP) thymocytes into fully mature recirculating peripheral T cells is both poorly understood with regard to the expression of restricted isoforms (CD45R) of the leukocyte common antigen and in terms of T cell function. The present investigation monitored the extrathymic development of CD4+CD8- SP thymocytes in euthymic recipients using allotype-marked donor cells and monoclonal antibody OX22 which recognizes an epitope on the C exon of rat CD45R. We established that donor-derived cells in the blood 1 day later bore the phenotype of the injected SP thymocytes (CD4+ Thy-1+ CD45RC-). T cells with the identical phenotype were also present in the thoracic duct lymph of uninjected rats, suggesting that the Thy-1+ CD45RC- T cells represent recent thymic emigrants (RTE) which have migrated to the periphery of their own accord. During extrathymic maturation donor-derived peripheral RTE lost Thy-1 within 3 days and expressed the CD45RC+ high molecular weight isoform by day 7; between days 8 and 14 a proportion (25%-30%) of the donor cells once again lost the high molecular weight isoform (CD45RC-). The transition of SP (CD45RC-) thymocytes to fully mature CD45RC+ CD4 T cells via intermediate peripheral RTE was accompanied at each stage by an increased ability of the maturing T cells to induce skin allograft rejection. Unexpectedly, the subsequent loss of the high molecular weight isoform, following presumed antigen encounter, was associated with a significant reduction in the ability of this Thy-1-CD45RC- subpopulation to effect graft rejection. The cyclic expression of CD45RC isoforms on both immature and mature CD4 T cells and the fact that the low molecular weight isoform was found in the periphery on both RTE (unquestionably naive) and antigen-experienced CD4 T cells, makes it unlikely that this isoform uniquely identifies memory T cells, at least in the rat.

Animals↗
PubMed2002

Recent thymic emigrants and prognosis in T- and B-cell childhood hematopoietic malignancies.

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 in childhood B-cell acute lymphoblastic leukemia (ALL) or healthy controls because the former category may reflect compromised thymic function. From the Greek national childhood leukemia/lymphoma database we obtained all 30 available T-cell leukemia/non-Hodgkin's lymphoma cases, 30 age- and sex-matched childhood B-cell origin cases of ALL and 60 healthy hospital controls. We compared TREC levels in PBMCs using a real-time PCR assay. There was highly significant reduction of TREC values in children with T-cell malignancies (median 3,100 TRECs/10(6) PBMCs), whereas children with B-cell origin ALL had slightly but nonsignificantly lower TREC values compared to healthy children (medians 19,300 and 22,500 TRECs/10(6) PBMCs, respectively). During a median follow-up period of about 19 months, only 4 children died. All of them had a T-cell hematopoietic malignancy and relatively low TREC values. The number of TRECs was higher among healthy girls than among healthy boys, and a similar pattern was evident in T-cell malignancies. It appears that there is a pattern of concordance of high TREC values with better disease prognosis in hematologic childhood malignancies. This applies to specific disease entities with better prognosis (B-cell origin ALL having higher TREC values than T-cell leukemia/lymphoma) and to gender, another important predictor of prognosis conditional on disease entity (girls having higher TREC values than boys); however, it may also be true for the survival of individual patients. These preliminary findings can be used as hypothesis-generating indications that should be confirmed in larger data sets.

Age of Onset↗
PubMed1985

Antileukocyte activity I. Systemic inhibition of cellular emigration following local inflammation.

Inflammation in progress at one site decreases edema formation at a second and separate inflammatory focus. This clinically important phenomenon is known as counter-irritation. Since its effect on leukocyte responses has not been defined, we investigated in rats the systemic anti-inflammatory effect of local irritant injection on cellular emigration, particularly monocytes. Macrophage accumulation at a subcutaneous inflammatory site was severely depressed by prior intraperitoneal irritant injection despite continued macrophage accumulation in the peritoneal cavity and normal circulating monocyte levels. The phenomenon also existed in the peritoneal cavity to subcutaneously administered irritants and involved PMNs as readily as macrophages. Anti-inflammation occurred only when the counter-irritant was injected before or simultaneously with the measured inflammatory response while the degree and duration of inhibition depended upon the nature and amount of counter-irritant injected. These studies demonstrate that local inflammation inhibits leukocyte reactivity. Transplantation of syngeneic tumor but not normal cells also produced a depression in macrophage inflammatory responses. This inhibition differed from counter-irritation by not affecting granulocytes and by being transient despite tumor persistence.

Animals↗
PubMed1978

In-vivo effects of anti-inflammatory and other drugs on granulocyte emigration in the rabbit skin collection chamber.

A method for measuring localised leukocyte mobilisation under in-vivo conditions with a plastic skin collection-chamber adapted to the rabbit ear was used for assessing the effects of anti-inflammatory and other agents on granulocyte emigration. Studies on the effect of oral drug administration to rabbits indicated that most anti-inflammatory drugs, two cystostatic agents (cyclophosphamide and colchicine), but none of the other compounds exhibiting antihistaminc, beta-adrenolytic or neuroleptic properties, significantly inhibited granulocyte mobilisation. The results after topical application of some of these agents into the chamber correlated well with those obtained after oral treatment. This technique may thus prove useful in selecting new compounds inhibiting granulocyte mobilisation in acute inflammatory reactions.

Animals↗
PubMed1999

Ventrally emigrating neural tube cells differentiate into heart muscle.

A population of ventrally emigrating neural tube cells has been shown to migrate along the vagus nerve and contribute to the development of the gastrointestinal tract. Since the vagus also goes to the heart, we sought to determine if these cells migrated into the heart. Neural tube cells were tagged with replication-deficient retroviral vectors containing the LacZ gene, to permanently label their progeny. The virus was microinjected into the lumen of the caudal hindbrain of chick embryos on day 2. Embryos were later processed for the detection of LacZ positive cells. Labeled cells were initially confined to the neural tube. Later, they migrated in association with the vagus nerve into the heart, where they were located in the myocardium. Labeled cells were identified as cardiac muscle cells of non-neural crest origin, with specific markers. It is concluded that some cardiac muscle cells differentiate from the neural tube cells.

Animals↗
PubMed1996

Scatter factor/hepatocyte growth factor (SF/HGF) induces emigration of myogenic cells at interlimb level in vivo.

The initiating event in the migration of myogenic cells to the limb buds is an epitheliomesenchymal transformation of cells located at the lateral edge of the dermomyotome. Recently, a targeted mutation of c-met in mice demonstrated an essential role of this tyrosine kinase receptor and its ligand, scatter factor/hepatocyte growth factor (SF/HGF), in the migration of myogenic cells to the limb buds. Here, we show that ectopic application of exogenous SF/HGF induces emigration of Pax-3-positive myogenic cells into the lateral plate mesoderm. During this process, the lateral portions of the dermomyotomes deepithelialize and the basement membrane disintegrates. Detaching myogenic cells do not lose N-cadherin from their surfaces. We conclude that an HGF/SF- and c-met-mediated signal detaches myogenic precursor cells from the somites and thus plays a necessary role in the initiation of myoblast migration.

Animals↗
PubMed1989

Epidermal tissue homeostasis: apoptosis and cell emigration as mechanisms of controlled cell deletion in the epidermis of the toad, Bufo bufo.

In normal, non-expanding toad epidermis more cells are produced than needed to replace cells lost by moulting. By implication, cell deletion additional to moulting must take place. This paper deals with the mechanisms by which the "surplus" of cells is deleted, taking advantage of the fact that the ratio between cell birth rate (Kb) and the rate of desquamation (Kd), which in normal toads is 2 to 3, can be manipulated. In toads deprived of the pars distalis of the pituitary gland it is decreased to 0.2 to 0.3, and in toads with hydrocortisone pellets implanted into the subcutaneous lymph space it is increased to 7 to 10. Thus, structures candidates for the morphological manifestation of the deletion process should occur rarely in toads in which the pars distalis has been removed and frequently in toads with hydrocortisone pellets implanted. Categorization and enumeration of such structures by light microscopy in the epidermis from operated, normal, and hormone-treated toads were performed. The incidence of structures referred to as "dark cells" and "omega-figures" were found to correlate relatively well with the Kb/Kd-ratio. A subsequent ultrastructural analysis - on a cell-by-cell basis - of "dark cells" showed these to reflect various stages of apoptosis. The duration of the apoptotic process was calculated to be approximately 7 h. Light- and electron microscopy of "omega-figures" combined with histochemical observations of PSA-lectin binding were interpreted as reflecting a release of cells from the basal epidermis and their final elimination within the dermis. It is concluded (i) that apoptosis is an important mechanism of controlled cell deletion, (ii) that emigration to, and elimination in, the dermis is a possible deletion mechanism, and (iii) that necrosis is unlikely to play a role in controlled cell deletion.

Animals↗
PubMed1984

The emigration of lymphocytes from palatine tonsils after local labelling.

Lymphocytes in the palatine tonsils of normal young pigs were selectively labelled by minute multiple injections of fluorescein isothiocyanate into the tonsils. One day later the numbers of tonsil-derived lymphocytes were determined in cervical, bronchial and mesenteric lymph nodes, spleen, Peyer's patches, thymus, bone marrow and blood. Although not all tonsillar lymphocytes could be labelled by this technique, a total of approximately 0.6 X 10(9) lymphocytes emigrated from the tonsils. Relatively more lymphocytes were found in lymph nodes than in the spleen and very few in the thymus, Peyer's patches and bone marrow. This organ distribution was different from the results from selectively labelling lymphocytes in lymph nodes, spleen and bone marrow.

Animals↗
PubMed1976

Effect of hog anaphylatoxin (C 5a) on vascular permeability and leukocyte emigration in vivo.

The effects of highly purified hog anaphylatoxin (C 5a) on leukocyte emigration were investigated in guinea pigs in vivo using two experimental models: 1. Subcutaneous infusions. Sterile solutions of C 5a in saline infused at a rate of 1.8 mug C 5a/h (0.2 ml/h) for 10 h induced a dense accumulation of leukocytes, mainly neutrophils but also some eosinophils at the site of application; In control infusions with saline alone comparatively few leukocytes were found. 2. Single injections into the pleural cavity. 10 or 20 mug C 5a (dissolved in 2 ml saline) caused a dose-dependent increase in leukocyte number and volume of pleural exudate. Bradykinin in a dose of 18 mug produced similar fluid exudation as 20 mug C 5a but had no significant effect on leukocyte accumulation. Intrapleural injections of C 5a further caused the appearance of i.v. injected Evans blue in the pleural cavity. This effect, indicating an increase in vascular permeability lasted for about 3 h; Since at least one of the two models used - subcutaneous infusion -simulates natural conditions -continuous local generation of C 5a in small amounts at the site of an inflammatory lesion-the results indicate that C 5a once formed by complement activation in natural defense reactions may contribute to local increase in vascular permeability and leukocyte infiltration.

Anaphylatoxins↗
PubMed1996

The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.

Animals↗
PubMedDate not supplied

Thymic function and output of recent thymic emigrant T cells during intracranial glioma progression.

One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naive T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4+ CD8+ (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8+ RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.

Animals↗
PubMed2001

T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation.

T cell differentiation in the thymus is characterized by a hierarchical order of rearrangement steps in the T cell receptor (TCR) genes, resulting in the joining of V, D, and J gene segments. During each of the rearrangement steps, DNA fragments between rearranging V, D, and J gene segments are deleted as circular excision products, the so-called TRECs (T cell receptor excision circles). TRECs are assumed to have a high over-time stability, but they can not multiply and consequently are diluted during T cell proliferation. It was recently suggested that quantitative detection of TRECs would allow for direct measurement of thymic output. The deltaRec-psiJalpha TREC appears to be the best marker, because the majority of thymocyte expansion occurs before this TREC is formed. However, apart from thymic output several other factors determine the TREC content of a T cell population, such as cell division and cell death. Likewise, the number of TRECs depends not only on thymic output, but also on the longevity of naive T cells. This warrants caution with regard to the interpretation of TREC data as measured in healthy and diseased individuals. deltaRec-psiJalpha TREC detection is a new and elegant tool for identification of recent thymic emigrants in the periphery, but further research is required for making quantitative estimations of thymic output with the use of TREC analysis.

Animals↗
PubMed2007

Intravesical Cu-T emigration: an atypical and infrequent cause of vesical calculus.

Transuterine transvesical emigration of an intrauterine contraceptive device is a rare and uncommonly described complication of an intrauterine device. We report and describe the clinical outcome and management of one such case of intravesical intrauterine device that had become calcified leading to the erroneous diagnosis of a vesical calculus. The diagnosis was confirmed after cystoscopic visualization, lithoclasty and extraction of the calcified plaque consisting of the Cu-T. A migrated IUD is a rare and infrequent cause for the formation of secondary vesical calculi. The treating surgeon should be aware of the possibility of such episodic cases of vesical calculi occurring in the women presenting with recurrent unexplained urinary sepsis.

Adult↗
PubMed1995

CD18-independent mechanism of neutrophil emigration in the rabbit lung after ischemia-reperfusion.

BACKGROUND: Reperfusion of ischemic lung causes an inflammatory pulmonary vascular injury characterized by increased vascular permeability and migration of inflammatory cells into the alveoli. Migration of neutrophils into the alveolus during reperfusion after 24 hours of unilateral pulmonary artery occlusion has been shown to be in part dependent on the CD18 adhesion molecule on the cell surface. The current study investigated whether reperfusion lung injury after a 1-hour period of complete lung ischemia was CD18 dependent. METHODS: Eighteen rabbits were assigned to one of three groups. Groups 1 and 2 were subjected to one hour of in situ right hilar occlusion followed by 2 hours of reperfusion. Group 3 was subjected to identical surgical dissection but the right hilum was never occluded. Group 1 rabbits received saline solution (1 mL/kg) before hilar occlusion and group 2 rabbits, monoclonal antibody 60.3, a blocking antibody for the CD18 adhesion molecule on the neutrophil surface (2 mg/kg). In 3 of the antibody-treated rabbits, flow cytometry was performed on blood neutrophils before and after administration of the antibody and 120 minutes after reperfusion. RESULTS: The rabbits in groups 1 and 2 had significantly increased alveolar neutrophil infiltrate and increased pulmonary vascular resistance compared with the rabbits in group 3. However, there was no significant difference between group 1 (saline solution treated) and group 2 (antibody treated). Antibody treatment did not block migration of neutrophils into the alveoli. Flow cytometry of circulating neutrophils demonstrated that CD18 was upregulated after reperfusion and that CD18 was fully blocked after antibody treatment for the duration of the study. CONCLUSIONS: We conclude that a 1-hour period of warm ischemia followed by reperfusion results in upregulation of CD18 but that emigration of the neutrophils into the alveoli is not CD18 dependent in this injury.

Animals↗
PubMed1992

Branching process with emigration--a genetic model.

Solution of a genetic improvement problem under the model of assortative mating is proposed. This has been achieved through the technique applied to a branching process incorporating a generation-dependent emigration component. The model explains a population subject to culling against genes governing undesirable characters and this work has been tried for a diploid population with two alleles at a single locus, which may be extended to the multilocus case.

Animals↗