UNIPROT:P14784 - FACTA Search

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Query: UNIPROT:P14784 (IL-2 receptor)
3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a recently developed murine model of haematogenously induced Staphylococcus aureus, the authors have characterized the phenotypes and functional properties of inflammatory cells present in the synovium of arthritic mice. The results show that large numbers of granulocytes and macrophages were observed in the inflamed synovia within 24 h of inoculation of S. aureus strain LS-1. Many of the synovial macrophage-like cells strained for cytoplasmic IL-1 alpha and TNF-alpha. Subsequently (> or = 48 h later), a prominent infiltration of T lymphocytes, predominantly of CD4+ phenotype, was observed. Some of the T lymphocytes stained for IL-2 receptor and intracytoplasmic interferon-gamma (IFN-gamma). Surprisingly, in spite of the severe inflammatory process, very few cells expressed MHC class-II molecules in the arthritic synovia. In addition, in vivo depletion of CD4+ T-cells resulted in a considerably milder course of staphylococcal arthritis. The similarities in the phenotype expression of synovial cells and central role of T-cells in S. aureus arthritis as well as in non-infectious models of arthritis, indicate that the process governing joint destruction is likely to be the same, irrespective of the initial stimulus.
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PMID:Role of T lymphocytes in experimental Staphylococcus aureus arthritis. 814

Treatment of pregnant Long Evans rats with benzodiazepines was found to cause alterations in cellular immune responses in their offspring. We now report on changes in interleukin-1 (IL-1) and IL-2 secretion which were analyzed in rats from birth until 12 weeks. Time-pregnant rats were treated with diazepam (1.25 mg/kg/day subcutaneously) from gestational day 14 to 20. Lipopolysaccharide-stimulated release of macrophage-derived IL-1 by spleen cells, determined on D10.G4.1 cells, remained in the control range during the preweaning period (postnatal day 6-28), then decreased in prenatally diazepam-exposed offspring, significantly in males during the postweaning period (postnatal day 34-61) and in both sexes in adults (postnatal day 62-83). Concanavalin A-stimulated release of T lymphocyte-derived IL-2 from spleen cells, determined on CTLL-2 cells, was reduced in male and female offspring during preweaning (postnatal day 3-28) and postweaning (postnatal day 33-55) periods and normalized in adulthood (postnatal day 60-84). The percentage of IL-2 receptor expressing (CD25+) cells was unaffected. From these and our earlier data it is evident that prenatal exposure to low doses of benzodiazepines can result in long-lasting alterations of the cytokine network, as indicated by reduced release of TNF-alpha, IL-1, IL-6, IL-2 and interferon-gamma. The concomitant reduction of peripheral type benzodiazepine receptors on macrophages is discussed as a possible link between prenatal treatment and disturbed function.
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PMID:Diazepam treatment of pregnant rats differentially affects interleukin-1 and interleukin-2 secretion in their offspring during different phases of postnatal development. 815 57

We have previously reported that transforming growth factor-beta 1 (TGF-beta 1) inhibits interleukin-6 (IL-6) induction by IL-2 and IL-1 in fresh human monocytes. We investigated the effects of TGF-beta 1 on the expression of tumoricidal activity induced by IL-2 or interferon-gamma (IFN-gamma) in human monocytes. We showed that TGF-beta 1 specifically inhibited, in a dose-dependent manner, IL-2-induced but not IFN-gamma-induced monocyte tumoricidal activity. The inhibitory effects of TGF-beta 1 on IL-2-activated monocytes were not caused by down-modulation of the IL-2 receptor beta (IL-2R beta) because the treatment of monocytes with IL-2 and TGF-beta 1 increased IL-2R beta mRNA expression. However, we found that TGF-beta 1 down-modulated IL-2-induced IL-2R gamma mRNA, which may be responsible for the TGF-beta 1 inhibition of monocyte activation by IL-2. The resistance of the IFN-gamma-induced activation to the inhibitory effects of TGF-beta 1 could be caused by the ability of IFN-gamma to decrease TGF-beta 1 receptor expression, as shown by cross-linking experiments. Overall, these results showed that TGF-beta 1 is a powerful inhibitor of IL-2- but not of IFN-gamma-induced activation of monocytes to a cytotoxic stage. This differential effect may be attributed to modulation of cytokine receptor expression.
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PMID:Inhibitory cytokine circuits involving transforming growth factor-beta, interferon-gamma, and interleukin-2 in human monocyte activation. 819 69

Recent observations have demonstrated the presence of activated T lymphocytes and macrophages in human atherosclerotic lesions. Cells found within these lesions produce cytokines that alter vascular homeostasis in a manner that promotes atherogenesis. To elucidate the role of these immunocompetent cells in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic features of the cellular infiltrates was studied in normal aortas from children; and in later phases of the disease (including fatty streaks and fibrous or atheromatous plaques). Semi-quantitative analysis of cytokine-expressing cells was also investigated with serial sectioning. In 4 of 9 young subjects, the grossly normal aorta contained relatively cell-rich areas which were located preferentially around the ostia of intercostal arteries and were composed of isolated or layered T lymphocytes and macrophages. In these prelesional areas, interleukin-1 (IL-1), IL-2 receptor (IL-2R) and tumour necrosis factor (TNF) were detected in the cytoplasm of the infiltrating cells, whereas no detectable reactivity was noted for IL-2, IL-6, interferon-gamma (IFN-gamma) or lymphotoxin (LT). In fatty streaks and full-grown atheromas including "cap" and "shoulder" regions, various numbers of T lymphocytes, macrophages and macrophage foam cells were present. In these lesion areas, especially where the cellular infiltrates were numerous, macrophage foam cells and smooth muscle cells expressed not only IL-1 and TNF but also IL-6. The ratio of IL-2R positive cells showed a tendency to decrease with advance of the disease process. Electron-microscopic examination of lesion areas demonstrated ultrastructural aspects of the cognate cell-to-cell interaction, as shown by the direct apposition of lymphocytes to macrophages or macrophage foam cells. These results suggest that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherosclerosis.
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PMID:Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis. 829 Dec 16

Injection of a low dose of mercuric chloride into Brown Norway (BN) rats caused a marked decrease in the concanavalin A (ConA)-induced generation of interferon-gamma-producing cells (IFN-gamma pc) in spleen cell cultures prepared 1 h after mercury administration. A second injection 48 h later caused a further diminution of IFN-gamma pc down to 30% of the number generated in splenocyte cultures of phosphate-buffered saline (PBS)-injected controls. Injection of Lewis rats with either one or two doses of HgCl2 revealed no inhibitory effect on splenic IFN-gamma production. The presence of the reduced form of glutathione (GSH) in the culture medium was found to be essential in these experiments. In the absence of GSH there was an overall 20-fold reduction of the number of IFN-gamma pc in splenocyte cultures of normal or PBS-injected rats, which was further reduced to a 60- to 70-fold-lower level in cultures of rats exposed to HgCl2. This mercury-mediated extra reduction could be fully reversed with an excess (2 mM) of GSH in Lewis but not in BN splenocyte cultures. Since the bivalent Hg2+ ion is known to bind to and inactivate sulfhydryl groups of proteins and low molecular weight thiols, most notably GSH, we investigated a possible role for thiols in IFN-gamma production. It was found that the generation of IFN-gamma pc in normal BN and Lewis splenocyte cultures was strongly dependent on GSH or its precursor cysteine in the culture medium. Other thiol compounds were also effective but disulfides were completely inactive. Depletion of intracellular GSH in ConA-stimulated splenocytes by buthionine sulfoximide (BSO), an inhibitor of de novo GSH biosynthesis, strongly inhibited the generation of IFN-gamma pc. The inhibitory effect of BSO was not abolished by the addition of interleukin-2 (IL-2), but was mimicked with antibodies directed to the IL-2 receptor. The data stress the importance of GSH in the enhancement of IL-2-mediated IFN-gamma production and are most consistent with a model in which mercury interferes with T cell IFN-gamma production by affecting the intracellular availability of GSH. The strain-specific susceptibility to mercury-mediated inhibition of IFN-gamma production is discussed.
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PMID:Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. 844 15

Varying the concentration of anti-CD3 immobilized on Sepharose beads allowed us to study both the inhibitory and the stimulatory effects of IL-4 on purified T cells and contrast IL-4 versus IL-2-driven T-cell proliferative responses. In the presence of low density immobilized anti-CD3, IL-4 was unable to stimulate purified T cells and was inhibitory to IL-2-driven T-cell responses. The inhibitory effects of IL-4 were enhanced by preincubation of T cells with IL-4 prior to stimulation. In contrast, the inhibitory effects of IL-4 could be avoided by delaying the addition of IL-4 until Days 3-5 of culture or they could be reversed by the addition of IL-1. In the presence of high-density anti-CD3, IL-4 elicited an IL-2-independent proliferative response by purified T cells or sorted CD8+ cells. Comparison of IL-4-driven versus IL-2-driven T-cell responses demonstrated that IL-2 was able to upregulate mRNA for IL-4 receptors and interferon-gamma, while IL-4 had minimal effects on upregulating mRNA for either the p55 or the p75 IL-2 receptor subunits or interferon-gamma. The timing of the presence of IL-4, the state of T-cell activation, and the nature and strength of the stimulatory signal influenced the regulatory effect of IL-4 on the immune response.
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PMID:Low versus high density of immobilized anti-CD3 influences IL-4 regulation of T-cell immune responses. 845 80

Cancer patients undergoing interleukin (IL)-2-based immunotherapy frequently experience dose-limiting side effects believed to be caused by the actions of such cytokines as IL-1 beta, tumor necrosis factor (TNF)-alpha and -beta, and interferon-gamma (IFN-gamma). Human peripheral blood mononuclear cells (PBMC) or monocyte-depleted peripheral blood lymphocytes were stimulated for up to 7 days by either of 2 IL-2 analogues (R38A or F42K) that bind to the intermediate-affinity IL-2 beta gamma receptor but have reduced abilities to bind the high-affinity IL-2 receptor. We previously reported that these IL-2 analogues retain the ability to generate lymphokine-activated killing by PBMC. In this study, we analyzed the cytokine content of supernatants from stimulated PBMC and peripheral blood lymphocyte cultures by enzyme-linked immunosorbent assay. The secretions of IL-1 beta, TNF-alpha, and -beta, and IFN-gamma induced by either R38A or F42K were markedly reduced compared with secretions produced in response to recombinant wild-type IL-2. In 4 experiments, secretion was reduced an average of 39% for IL-1 beta, 57% for TNF-alpha, 83% for TNF-beta, and 86% for IFN-gamma. Polymerase chain reaction analysis of recombinant wild-type IL-2 or analogue-stimulated PBMC did not reveal the presence of IL-2 mRNA; thus, differential production of endogenous IL-2 could not account for these findings. These data suggest the interaction of IL-2 and the high-affinity IL-2 receptor on human PBMC or peripheral blood lymphocyte is required for maximal secretion of IL-1 beta, TNF-alpha, TNF-beta, and IFN-gamma. Because such cytokines are believed to mediate the toxicity seen with IL-2-based immunotherapies, IL-2 analogues with reduced binding to the high affinity IL-2 receptor may prove to be an effective and less toxic means of cancer treatment.
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PMID:Human interleukin 2 analogues that preferentially bind the intermediate-affinity interleukin 2 receptor lead to reduced secondary cytokine secretion: implications for the use of these interleukin 2 analogues in cancer immunotherapy. 849 22

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 class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Using an in vitro antigenic stimulation model of murine spleen cells in the presence of the immunosuppressor cyclosporin A (CSA) we have previously reported that not only does this drug not interfere with the differentiation of T lymphocytes into memory cells it appears to favor this differentiation (Motta, I. et al., Eur. J. Immunol. 1991. 21:551). Because CSA blocks interleukin-2 (IL-2) gene expression, we have analyzed the effect of this cytokine on memory T helper cell development. Murine splenic cells were primed for 6 days with sheep red blood cells (SRBC) in protocols in which either IL-2 was not produced or its biological activity was neutralized by anti-IL-2 receptor (R) antibodies. The helper function of the recovered T cells was revealed by their capacity to help virgin B splenocytes produce anti-SRBC antibodies upon challenge in vitro. We found that CD4+ cells primed in the absence of IL-2, provoked either by IL-2 gene transcription blockade by CSA or by treatment with anti-IL-2R antibodies, afford the best helper functions. These cells exhibit a memory-type phenotype characterized by the low expression of the MEL-14 marker and the high expression of the CD44 marker. Evidence is also presented that memory T helper cells originate in part from naive subset displaying the MEL-14hi phenotype. The pattern of expression of the genes encoding different cytokines (IL-2, IL-4, IL-5 and interferon-gamma) following a secondary antigenic stimulation shows that the helper function of the cells primed in the absence of IL-2 correlates with the up-regulation of the IL-2 and the IL-5 genes. From these data, we conclude that IL-2 plays a major role in the control of memory T helper cell induction.
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PMID:Interleukin-2 down-modulates memory T helper lymphocyte development during antigenic stimulation in vitro. 856 29

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.
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PMID:Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis. 863 62

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