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Results for “ectopic T cell activation”

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At least 19 recordsLinked to original sources
PubMed1990

Genetic analysis of amylase-producing cell lines: ectopic activation of the amylase gene by translocation.

Two amylase-producing cell lines have been established, KMK-2 from a patient with gastric cancer, and KHM-1B from a patient with IgA lambda-type multiple myeloma. Both patients exhibited extremely high levels of serum amylase. The production of S-type amylase m-RNA by KMK-2 and KHM-1B was demonstrated by Northern blot analysis. Chromosome analysis showed many qualitative and quantitative abnormalities in both cell lines. In KHM-1B, a translocation was found between 1p13 or 21, near the amylase genes locus, and 9q34, the abl oncogene locus. These findings suggest the amylase gene in KHM-1B to be activated by translocation. A rearranged amylase gene was demonstrated by Southern blot analysis with only one enzyme, Accl.

Amylases↗
PubMed1991

Xenopus Myf-5 marks early muscle cells and can activate muscle genes ectopically in early embryos.

We have cloned a Xenopus cDNA that encodes a homologue of the human myogenic factor, Myf-5. Xenopus Myf-5 (XMyf5) transcripts first accumulate in the prospective somite region of early gastrulae. The pattern of XMyf5 expression is similar to that of the Xenopus MyoD (XMyoD) gene, except that XMyf5 transcripts are largely restricted to posterior somitic mesoderm even before any somites have formed. Transient ectopic expression of XMyf5 activates cardiac actin and XMyoD genes in animal cap cells, but does not cause full myogenesis, even in combination with XMyoD. These results suggest that XMyf5 acts together with XMyoD as one of the set of genes regulating the earliest events of myogenesis, additional factors being required for complete muscle differentiation.

Amino Acid Sequence↗
PubMed1992

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals↗
PubMed1988

Tartrate-resistant acid phosphatase activity in tibial osteoclasts and cells elicited by ectopic bone and suture implants in normal and osteopetrotic rats.

Bone-induced multinucleated cells have been suggested as surrogates for the study of osteoclastic lineage and function. This study evaluates this proposal by comparing acid phosphatase localization in tibial osteoclasts (in situ) with that of cell populations elicited by subcutaneous implantation of devitalized trabecular bone chips from two week old rats and suture into normal and osteopetrotic (ia) rats, emphasizing tartrate-resistant acid phosphatase, an osteoclastic marker. The ia rat mutation of osteopetrosis is characterized by defective osteoclasts which typically express enhanced TRAP activity when compared to normal; ia macrophage populations do not share the same osteoclastic defect and demonstrate normal amounts of acid phosphatase reactivity. The majority of the acid phosphatase activity expressed by implant-elicited mononuclear cells was tartrate sensitive. An increase in the percentage of tartrate-sensitive, but not TRAP-positive, mononuclear cells was observed during the 14-day implantation period, suggesting the mononuclear cells did not undergo osteoclastic differentiation. Both normal and ia osteoclasts contained high concentrations of TRAP reaction product (++) while bone- and suture-induced multinucleated cells examined at 14 days post-implantation were negative (0) or mildly (+) TRAP reactive. We conclude that devitalized bone matrix implanted at this ectopic site is capable of the formation of TRAP-positive (+) multinucleated cells, but when compared on the basis of strength of TRAP activity, the bone-induced multinucleated cells do not resemble active osteoclasts, but are similar to suture-elicited macrophage polykaryons. Therefore, we suggest caution in the use of bone-induced multinucleated cells as surrogates for the study of osteoclasts and normal bone resorption. Instead, these cells may represent a population of cells involved in pathological bone loss due to inflammation.

Acid Phosphatase↗
PubMed1990

Activation of muscle genes without myogenesis by ectopic expression of MyoD in frog embryo cells.

The sequence-specific DNA-binding protein, MyoD, can activate muscle-specific gene expression in some cells in culture. Xenopus MyoD (XMyoD) transcription is activated as a consequence of mesoderm induction in the early myotomes, from which the axial musculature develops. XMyoD RNA accumulates about two hours before muscle-specific actin transcripts first appear, and so is expressed at the right time and in the right place to play a part in activating muscle-specific gene expression in normal development. To test this idea, we have expressed XMyoD ectopically in early Xenopus embryos. We find that injection of XMyoD RNA can strongly activate muscle genes in embryo cells normally destined to form ectoderm. Nevertheless, these cells fail to differentiate as muscle, suggesting that additional factors are required for complete and stable myogenesis.

Amino Acid Sequence↗
PubMed1992

Ectopic corticotropin-releasing hormone produced by a transfected cell line chronically activates the pituitary-adrenal axis in transkaryotic rats.

Hypothalamic CRH is the primary positive regulatory factor of the pituitary-adrenal axis. The purpose of our study was to analyze the chronic effects of CRH on the production and secretion of POMC peptides from both the anterior lobe (AL) and neurointermediate lobe (NIL) of the pituitary by mimicking the syndrome of ectopic CRH secretion from neuroendocrine tumors. We first generated stably transfected W2 medullary thyroid carcinoma cell lines with a rat CRH expression vector under the transcriptional control of a cytomegalovirus gene promoter. These cell lines constitutively expressed the foreign gene, accurately processed the encoded prepro-CRH, and secreted biologically active CRH with an estimated potency equivalent to that of synthetic CRH-(1-41)NH2. The cell line designated W2CRH-7 was implanted sc in the syngeneic rat strain WAG/Rij and produced tumors that abundantly secreted CRH into the peripheral circulation. Four weeks postimplantation, W2CRH-7, but not wild-type W2, cells caused significant increases in the AL content of beta-endorphin-like immunoreactivity comparable to that caused by adrenalectomy (ADX). Plasma ACTH and serum beta-endorphin-like immunoreactivity were increased to a greater extent by ADX than by W2CRH-7 cell implantation. The NIL of both male and female rats showed either no change or a tendency to decreased beta-endorphin concentrations with no change in the acetylation or carboxy-shortening profiles judged by cation exchange chromatography in response to the ectopic CRH treatment. Rats of both sexes maintained a profound activation of the pituitary adrenal axis up to 16 weeks postimplantation, with normalized adrenal gland weights 5 times that of controls. The chronic secretion of CRH by W2CRH-7 cells resulted in a complete cessation of body growth in all rats up to the maximum time tested of 16 weeks. The lack of growth was partly ameliorated by concomitant ADX, suggesting an important role for adrenal glucocorticoids in these effects. We conclude that 1) the transplantable W2CRH-7 cell line provides a highly effective and reproducible means of sustained CRH treatment that mimics the syndrome of ectopic CRH expression by neuroendocrine tumors; 2) AL corticotrophs respond to chronic CRH by a sustained production and secretion of POMC peptides, leading to a marked adrenal cortical hyperplasia, with no evidence of biologically significant desensitization; 3) chronic CRH tends to decrease the NIL content of beta-endorphin,with remarkably little effect on posttranslational processing; and 4) the syndrome of chronic ectopic CRH in WAG/Rij rats includes a cessation of body growth at least partly due to products of the adrenal glands.

Adrenalectomy↗
PubMed1978

Nonspecific signals for B-cell localization and activation.

Virgin, inactive mammary gland autografted to the anterior chamber of the rabbit eye remains free of lymphoid cells. Activation of the ectopic gland by systemic injection of chorionic gonadotropin results in maturation of the gland and milk production, accompanied by the immirgration of lymphocytes and their activati-n to Ig formation, predominantly of the IgA class. In the presence of antigen-induced intraocular inflammation, the activated gland is able to influence the Ig class of B cells in the neighboring ocular tissues. These data suggest that even nonlymphoid tissues may elaborate lymphocyte-homing and polyclonal B-cell activating factors which function independently of specific antigen.

Animals↗
PubMed2026

Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is primarily driven by a Type 2 immune response, with T helper (TH2) cells producing IL-4 and IL-13, thereby promoting inflammation, itch, and a compromised skin barrier. Yet, the spatial organization of pathogenic immune cells and their interactions with stromal and epithelial compartments in human AD skin remain incompletely understood. METHODS: We performed 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies from patients with AD (n = 6), psoriasis (n = 2), and healthy controls (n = 5). Data were integrated with AD single-cell RNA sequencing (scRNA-seq) datasets and complemented by imaging mass cytometry (IMC) and multiplex immunofluorescence (IF) to validate the spatial localization of immune cells. Cell-cell communication analysis revealed putative signaling interactions within immune niches. RESULTS: Spatial clustering resolved tissue compartments and demonstrated transcriptional dysregulation in keratinocytes in AD and psoriasis. AD lesions showed a conserved spatial organization of immune aggregates within the superficial dermis. Integration of scRNA-seq signatures revealed spatially organized co-localization of T cells and mature migratory dendritic cells (mmDCs). We developed a ring-based neighborhood analysis to characterize the cellular organization of the immune-stromal niches, revealing T cell-enriched regions surrounded by inflammatory fibroblasts and activated keratinocytes. Intercellular communication analysis further identified putative signaling within mmDC-T cell niches that may promote pathogenic T cell recruitment and activation. Application of tertiary lymphoid structure (TLS) signatures indicated the presence of TLS-like regions. IMC and IF validated the close spatial proximity between activated TH2 cells and mmDCs. CONCLUSION: AD lesions contain spatially organized TLS-like immune niches at the dermal-epidermal junction, characterized by the close association of T cells and mmDCs and coordinated interactions with surrounding stromal and epithelial compartments. These mmDC-T cell niches may represent potential targets for future therapeutic strategies aimed at disrupting persistent local inflammatory pathways and improving long-term disease control.

atopic dermatitis↗
PubMed1992

Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity.

Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif. Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however. We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line. Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells. This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2-mediated enhancer activation. Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation. Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position. The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position.

Animals↗
PubMed1977

Histochemical distribution of delta5-3beta- and 17beta-hydroxysteroid dehydrogenases in hamster trophoblast.

The histochemical distribution of delta5-3beta- and 17beta-hydroxysteroid dehydrogenases was demonstrated in hamster trophoblast between Days 8 and 15 of pregnancy. The delta5-3beta-hydroxysteroid dehydrogenase activity in the ectoplacental trophoblast of 8-day embryos was demonstrated by use of delta5-pregnenolone and dehydroepiandrosterone as substrates; between Days 11 and 15, activity was demonstrated in the trophoblastic giant cells of the placenta and in the intra-arterial trophoblast cells when delta5-pregnenolone was the substrate. Between Days 11 and 15, 17beta-hydroxysteroid activity was present in the spongiotrophoblast, labyrinth, placental giant cells and intra-arterial trophoblast cells, as shown by use of testosterone and oestradiol as substrates. Both enzymes were demonstrated in ectopic trophoblast cells, indicating that these activities are autonomous.

17-Hydroxysteroid Dehydrogenases↗
PubMed1991

A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells.

Oct-4 is a transcription factor expressed in the pluripotent progenitor cells of the early mouse embryo. Additional factors are required for the distal activation of genes in differentiated cells containing ectopically expressed Oct-4. Here we show that Oct-4 and E1A are sufficient for distance-independent activation of the basal transcription machinery. The ratio of Oct-4 to E1A is critical for transcriptional activation, because higher levels of either factor are less efficient. Activation depends on a transactivation domain linked to the POU domain of Oct-4 and also on the conserved domain 3 of the 289RE1A protein. This domain is required for binding to the C-terminal part of Oct-4 including the POU domain. Our results indicate that E1A can serve as a bridging factor between Oct-4 and the basal initiation complex, and we postulate that an E1A-like factor acts as a cellular bridging factor of Oct-4 in pluripotent cells.

Adenovirus Early Proteins↗
PubMed1990

An autoregulatory enhancer element of the Drosophila homeotic gene Deformed.

The stable determination of different anterior-posterior regions of the Drosophila embryo is controlled by the persistent expression of homeotic selector genes. One mechanism that has been proposed to explain the persistent expression of the homeotic gene Deformed is an autoactivation circuit that would be used once Deformed expression had been established by earlier acting patterning genes. Here we show that a large cis-regulatory element mapping approximately 5 kb upstream of the Deformed transcription start has the properties predicted for a Deformed autoregulatory enhancer. This element provides late, spatially localized expression in the epidermal cells of the maxillary and mandibular segments which is wholly dependent upon endogenous Deformed function. In addition, the autoregulatory enhancer can be activated ectopically in embryos and in imaginal disc cells by ectopic expression of Deformed protein. Deletion analysis of the autoregulatory element indicates that it contains compartment specific sub-elements similar to those of other homeotic loci.

Animals↗
PubMed1991

Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration.

Immunoglobulin (Ig) gene promoters contain the octamer sequence motif ATGCAAAT which is recognized by cellular transcription factors (Oct factors). Besides the ubiquitous Oct-1 factor, there is also a group of related factors (Oct-2 factors) encoded by a separate gene. The Oct-2 gene is regulated in a cell-type specific manner, and the protein is present in large amounts in B lymphocytes. We have previously shown that simple composite promoters of an octamer/TATA box type are poorly active in non-B cells but are strongly responsive to ectopic expression of Oct-2A factor, a major representative of the lymphocyte Oct-2 factors. In the present study we have tested the activity of a number of composite promoters and natural Ig promoters, and their response to Oct-1 and Oct-2 factors. Unexpectedly, we find that octamer/TATA promoters with a high affinity octamer site direct ubiquitous expression. By contrast, promoter constructions that behave in a B cell-specific manner tend to have a weak octamer binding site. These promoters are responsive to ectopic expression of additional Oct-factor, irrespective of whether it is Oct-1 or Oct-2. Using natural Ig promoters rather than composite promoters, we find that an IgH promoter is well transcribed in non-B cells via the ubiquitous Oct-1 factor, while Ig kappa and Ig lambda light chain promoters require additional Oct factor for maximal expression. It seems therefore likely that during B cell differentiation, Ig heavy chain promoters can be activated by Oct-1, before the appearance of Oct-2 factors. Oct-2 factors then would serve to boost the expression from Ig light chain promoters, which are known to be activated only after successful heavy chain gene rearrangement.

Autoradiography↗
PubMed1988

Immunohistochemical study of blood group activities in the alimentary canal in normal and pathologic conditions with reference to the nature of epithelial mucopolysaccharides.

ABO(H)- and Lewis-activities in the human alimentary canal were investigated by the avidin-biotin-peroxidase complex method using commercial mouse monoclonal antibodies in order to clarify (1) the changes apparent in these activities in carcinoma of the digestive tract or premalignant intestinal metaplasia of the stomach and (2) the relationship of the activities to the histochemical properties of epithelial mucins examined by Alcian blue (pH 2.5)/periodic acid-Schiff (PAS) double staining. In intestinal metaplasia, ectopic goblet cells showed various degrees of ABO(H)-activities according to the PAS stainability of mucins and revealed Lea-activity even in a Le(a-b+) group. In carcinoma of the alimentary canal, ABO(H)- and Lewis-activities compatible with the donors' blood groups were located mainly at the PAS-positive cell surface, and in the Golgi bodies and secretions. It was thus concluded that quantitative and/or qualitative changes in blood group activities were closely associated with those of epithelial mucopolysaccharides.

ABO Blood-Group System↗
PubMed2025

How to Study Gene Expression and Gain of Function of Hoxb1 in Mouse Heart Development.

Anterior Hox genes are required for genetic identity and anterior posterior patterning of the second heart field (SHF), which contributes to the formation of the embryonic heart in vertebrates. Defective contribution of SHF cells to the arterial or venous pole of the heart is often associated with severe congenital heart defects. The mouse Cre-lox system allows the activation of expression of any gene of interest in restricted tissues. We developed a gain of function approach that relies on the use of a CAG transgene to ectopically activate Hoxb1 expression in SHF cardiac progenitor cells through specific Cre activation. Therefore, we generated a floxed transgenic mouse line, CAG-Hoxb1-eGFP, which upon recombination by Cre recombinase conditionally induces robust Hoxb1 and eGFP expression. When induced within the anterior SHF lineage, we detected heart defects in mouse embryos such as right ventricular hypoplasia. Here, we describe the strategy for generating and genetically crossing this transgenic mouse line. We also provide detailed protocols for whole-mount embryo and paraffin section in situ RNAscope hybridization and X-gal staining allowing investigation of SHF contribution during heart development.

Animals↗
PubMed1990

Effects of propane-2, 2-diphosphonate (PDP) on matrix-induced ectopic bone formation in comparison to ethane-1-hydroxy-1, 1-diphosphonate (EHDP).

The most prominent effect of propane-2, 2-diphosphonate (PDP) and ethane-1-hydroxy-1, 1-diphosphonate (EHDP) on matrix-induced ectopic bone in the rat was a dose-dependent inhibition of osteogenesis in the early phases of development. The delay was seen as a consequence of osteoprogenitor cell inhibition. Additionally, later phases of bone maturation were disturbed by interference with the mineralization and remodeling processes. However, direct effects on the calcium phosphates of bone are only of minor additional value, which remains of lesser importance in comparison to the cellular impairment. After withdrawal of diphosphonates, the effects were nearly completely remitted. Neither PDP nor EHDP, even given in high doses, resulted in a lasting reduction in ectopic mass. The remission may be referred to the recovery of cell activities, whereas the mineral impregnation of osteoidosis was, if at all, of little importance. For treatment of ectopic osteogenesis PDP proved inefficient.

Animals↗
PubMed1990

Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells.

In non-lymphoid cells such as HeLa cells, ectopic expression of the lymphocyte-specific transcription factor Oct-2A can activate reporter genes whose promoters consist of a single octamer sequence (ATTTGCAT) upstream of a TATA box. While the factor is strongly active in a promoter position, it tails as an enhancer factor: an enhancer consisting of multiple copies of the octamer sequence placed downstream of the reporter gene is not active in HeLa cells, even at high concentration of Oct-2A. In B lymphoid cells, however, the same enhancer is highly active. This could mean that an additional factor is required for enhancer activation in B cells. Furthermore, we have tested the transcriptional activation potential of Oct-2A with a series of N-terminal and C-terminal deletions. We show that a glutamine-rich domain near the N-terminus is required for full activity. Otherwise, large segments of the N-terminal half or the entire C-terminal region are dispensable in our assay, as long as the deletions do not impinge on the conserved POU domain which is sufficient for DNA binding. While N-terminal and C-terminal regions can functionally compensate for each other, a combined deletion that only retains the POU domain is a strong down mutation. We also find that activity depends on the promoter structure of the reporter gene: the POU domain by itself shows some activity with a promoter where the octamer sequence is located very close to the TATA box, but no activity with another promoter construction where the octamer sequence is located further upstream. The two promoters also respond differently to the deletion of the glutamine-rich stretch important for transcriptional activation. From these experiments we consider it likely that the natural octamer factor variants can selectively activate the different naturally occurring octamer-containing promoters.

Amino Acid Sequence↗