Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we reported the isolation of a cDNA clone that encodes a polypeptide which has B cell and T cell growth factor activities. The amino acid sequence of this polypeptide deduced from the nucleotide sequence of the cDNA clone showed significant homology with mouse B cell stimulating factor-1. Because of its multiple biologic activities, it was designated interleukin 4 (IL-4). Here we describe the effects of supernatants of Cos-7 mouse cells transfected with the IL-4 coding cDNA clone in a mammalian expression vector, on human thymocyte T cells and T cell clones. The T cell growth-promoting effect of IL-4 on preactivated T cells was not inhibited by monoclonal antibodies against IL-2 or the IL-2 receptor, indicating that the IL-4 activity is independent from IL-2 or the IL-2 receptor. IL-4 induces a low proliferative response in thymocytes and peripheral blood lymphocytes, but the response was considerably enhanced by preactivation of the thymocytes or peripheral blood T cells. Both T4+ and T8+ antigen-specific proliferative and cytotoxic T cell clones and T3 natural killer clones proliferated in response to IL-4. But one of six T4+ and one of four T8+ T cell clones were consistently found to be unresponsive. The proliferative responses to IL-4 were always lower than those obtained with IL-2. Most of the T cell clones generally became unresponsive to IL-4 10 days after stimulation, but still responded well to IL-2. These results indicate that the responsiveness to IL-4 is relatively short lasting and is regulated by activation signals. Interestingly, IL-4 acted in synergy with IL-2 in promoting the growth of T cell clones. Our results establish that IL-4 can act as a T cell growth factor independently of IL-2.
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PMID:Recombinant interleukin 4 promotes the growth of human T cells. 349 96

The thymus is regarded as the primary site for T-cell lymphopoiesis, but very little is known about the lineage inter-relationships of cells within that organ. At least four subpopulations of mouse thymocytes can be defined on the basis of staining with monoclonal antibodies directed against the T-cell differentiation antigens Lyt-2 and L3T4 (ref. 2). Thus immunocompetent (medullary) thymocytes, like peripheral T cells, express either Lyt-2 (cytotoxic phenotype) or L3T4 (helper phenotype) but not both, whereas non-functional (cortical) thymocytes express both markers. In addition, a small subpopulation comprising 2-3% of cells in the thymus and expressing neither Lyt-2 nor L3T4 has recently been described. The latter cells have the properties of intrathymic 'stem cells' in that they are the first to appear in the embryonic thymus and at least some can be shown to give rise, both in vivo (ref. 4. and our unpublished data) and in vitro, to other thymocyte subpopulations. We show here that 50% of Lyt-2-/L3T4- cells in the adult thymus express receptors for the polypeptide growth hormone interleukin-2 (IL-2) whereas other cells in the thymus do not. Furthermore, immunohistochemical localization studies on frozen sections indicate a disperse distribution of IL-2 receptor-positive cells in both the cortex and medulla. These novel findings have potential implications in the context of current models of differentiation pathways within the thymus.
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PMID:Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. 391 12

Interleukin-2 (IL-2) is a T-cell-derived polypeptide hormone of 133 amino acids which exerts its growth-promoting activity via a surface receptor. Originally, IL-2 was believed to be a unique growth factor for activated T cells; more recent studies, however, have demonstrated that certain B-cell tumours as well as normal activated B lymphocytes express a surface molecule which is recognized by monoclonal antibodies directed against the IL-2 receptor. Furthermore, we and others have shown recently that activated B cells proliferate in response to either immunoaffinity-purified or recombinant IL-2. These controversial findings prompted us to undertake a detailed quantitative comparison of IL-2 receptor expression on activated B and T cells. We show here, using biosynthetically labelled IL-2(3H-IL-2) and anti-IL-2 receptor antibody (3H-PC61) that activated B and T cells express both high-affinity (apparent dissociation constant, Kd approximately 20 pM) and low-affinity (Kd approximately 1,000 pM) IL-2 receptors. Binding of IL-2 to both classes of receptor is inhibited by the monoclonal anti-IL-2 receptor antibody PC61. B blasts express half as many total IL-2 binding sites or PC61 binding sites as T blasts, and the ratio of the number of low- to high-affinity receptors for each cell type is approximately 10:1. Immunoprecipitation analysis of surface-labelled blasts indicates that B and T cells have IL-2 receptors of similar relative molecular mass. Taken together, these data suggest strongly that IL-2 can act as a growth hormone for both B and T lymphocytes.
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PMID:Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. 392 47

The design and construction of a new class of recombinant therapeutic agents, receptor-specific cytotoxins, has occurred within the last 5 years. Development of a number of receptor-targeted fusion toxins has been based on a detailed understanding of the structure-function relationships of both diphtheria toxin and Pseudomonas exotoxin A, and availability of the nucleic acid sequences of each structural gene. A variety of fusion toxins in which the native receptor-binding domain of either diphtheria toxin or Pseudomonas exotoxin A has been genetically replaced with either a polypeptide hormone or growth factor have been constructed. These fusion toxins selectively intoxicate receptor-bearing cells in vitro and are active in a variety of animal model systems. DAB486IL-2, and IL-2 receptor targeted cytotoxin, is the first fusion toxin to be evaluated in patients. Phase I/II clinical trials have been performed in refractory leukemia/lymphoma, severe rheumatoid arthritis, and Type 1 diabetes. DAB486IL-2 has been administered to more than 200 patients, has been well tolerated, and has shown encouraging signs of potential efficacy in all three clinical indications. Thus, DAB486IL-2 represents a new class of targeted biological therapeutic response modifiers whose mode of action is based on selective elimination of target cells.
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PMID:Recombinant fusion toxins--a new class of targeted biologic therapeutics. 810 49

Interleukin-2, a polypeptide lymphokine that induces proliferation of antigen- or mitogen-stimulated T cells, was first described as "T-cell growth factor" by Morgan et al. in 1976. IL-2 is one of several lymphocyte-produced messenger regulatory molecules that modulate immunocyte function. The main secretory source of IL-2 is the T-helper cell. In 1983, Taniguchi and colleagues isolated a human IL-2 complementary DNA clone from a high-producer Jurkat leukemic cell line, and established its nucleotide sequence. In 1984, Rosenberg et al. described the isolation of cDNA clones of the gene for IL-2 from the Jurkat cell line, its expression in Escherichia coli and its biological characteristics. The mature secreted protein contains 133 amino acids, constituting a calculated molecular weight of 15,420. Since the discovery of IL-2 and its T-cell growth-promoting activity, extensive research has revealed the complex nature of its immunologic effects, both in vitro and in vivo. The immunopotentiating activities, encouraging in vitro results, plus successful therapy of animal tumors in preclinical studies provided the rationale for investigation of IL-2 in patients with advanced malignancy and immunodeficiencies. The IL-2 receptor has been found to have an unexpected by unusual structure in that it is composed of two separate chains designated alpha (p75) and beta (p55). Recently, it has been discovered the 3rd gamma-chain by Sugamura et al. Clinical trials of IL-2 in patients with cancer have been done by many researchers. The clinical trials has reviewed briefly.
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PMID:[Interleukin-2 (IL-2)]. 815

Cell line PER-423 was derived from the cells of a patient with an immature acute T-lymphoblastic leukaemia and the growth of this human cell line is strictly dependent on interleukin-2 (IL-2). PER-423 cells express the p75 (beta) subunit of the IL-2 receptor (IL-2R beta), while the p55 chain (IL-2R alpha) is not detectable by immunofluorescence. The analysis of the IL-2R revealed that it is of intermediate affinity and the median effective IL-2 concentration for PER-423 cells (EC50 value) was determined to be 1.44 +/- 0.29 nM. Chemical crosslinking studies showed that the receptor consists of one polypeptide of approximately 95 kDa as well as a doublet of 70 kDa and 60 kDa and does not include the IL-2R alpha-chain. The steady-state mRNA level for the p75 subunit was similar to that present in a cell line expressing an IL-2R alpha+ beta+, while only traces for the alpha-chain were detectable. PER-423 cells can be induced to express the alpha-chain of the IL-2R on the cell surface, concomitant with a much reduced EC50 level. Since cell line PER-423 is functionally dependent on IL-2, it provides an ideal model for IL-2 signal transduction studies and for investigations focusing on the requirements for ligand binding vs activation.
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PMID:Functional interleukin-2 receptor on a Tac negative human leukaemia T-cell line. 842 80

Fusion toxins are hybrid proteins consisting of peptide ligands linked through amide bonds to polypeptide toxins. The ligand directs the molecule to the surface of target cells and the toxin enters the cytosol and induces cell death. Ricin is an excellent candidate for use in fusion toxins because of its extreme potency, the extensive knowledge of its atomic structure and the lack of prior immunological exposure in patients. We synthesized a baculovirus transfer vector with the polyhedrin promoter followed sequentially from the 5' end with DNA encoding the gp67A leader sequence, the tripeptide ADP, IL-2 (interleukin-2), another ADP tripeptide and RTB (ricin toxin B chain) with lectin-site mutations W37S and Y248H. Recombinant baculovirus was generated in Sf9 insect cells and used to infect Sf9 cells. Recombinant IL-2-RTB[W37S/Y248H] protein (fusion protein of IL-2 with modifications W37S and Y248H) was recovered at high yields from day 6 insect cell supernatants, partially purified by affinity chromatography and reassociated with RTA (ricin toxin A chain). The fusion toxin was soluble, immunoreactive with antibodies to RTB, IL-2 and RTA and had a molecular weight of 80 kDa by SDS-PAGE. The molecule reacted poorly with asialofetuin, but bound strongly to IL-2 receptor based on selective cytotoxicity to IL-2 receptor bearing cells. The specific cytotoxicity could be blocked with IL-2 but not lactose. Thus, we report a novel targeted fusion toxin protein with full biological activity.
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PMID:Characterization of a ricin fusion toxin targeted to the interleukin-2 receptor. 893 Nov 31

A new fungal immunomodulatory protein (Fip) has been purified from the edible mushroom, Volvariella volvacea, and designated Fip-vvo. Analysis of the purified protein by SDS/PAGE followed by Coomassie Blue staining demonstrated that Fip-vvo is a single polypeptide with an apparent molecular mass of 15 kDa. Periodic acid/Schiff staining showed that this single polypeptide lacks carbohydrates. Using an in vitro bioassay measuring blast-formation stimulatory activity, Fip-vvo was shown to stimulate the maximum proliferation of human peripheral blood lymphocytes at a concentration of 5 microg/ml. Fip-vvo was capable of agglutinating rat red blood cells. Neither haemagglutination nor mitogenic activities were inhibited by mono- or dimeric sugars. In vivo, repeat administration of Fip-vvo greatly reduced the production of BSA-induced Arthus reaction in mice, whereas little effect was observed on the prevention of systemic anaphylaxis reactions. The selectively enhanced transcriptional expression of interleukin (IL)-2, IL-4, interferon-gamma, tumour necrosis factor-alpha, lymphotoxin and IL-2 receptor by Fip-vvo was also demonstrated by reverse transcriptase-PCR. This finding suggests that Fip-vvo exerts its immunomodulatory effects via cytokine regulation. In addition, the complete amino acid sequence of Fip-vvo was obtained by direct protein sequencing. This protein consists of 112 amino acid residues with a blocked N-terminal end and has a calculated molecular mass of 12667 Da not including the N-terminal blocking group. By gel filtration analysis, Fip-vvo exhibited a molecular mass of 26 kDa for the native molecules in PBS. This result indicates that native Fip-vvo is most likely a non-covalently associated homodimeric molecule.
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PMID:Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea. 916 52

The synthetic polypeptide copolymer-1 (Cop-1; Copaxone; Glatiramer Acetate) has been recently approved as an effective treatment in relapsing multiple sclerosis (MS). A large body of evidence demonstrates that Cop-1 induces active suppression of CNS-inflammatory disease in animal models. However, Cop-1-mediated suppressor mechanisms have not yet been elucidated in humans. A 12-month open study following clinical and immunological parameters of ten relapsing MS patients treated with Cop-1 is presented. Relapse rates and disability scores (EDSS) were evaluated prior to and after 12 months of treatment. The immunological parameters assessed prior to and at 3 months' interval during treatment included serum levels of soluble IL-2 receptor (sIL-2R) and IL-10 as well as leukocyte cytokine mRNA expression of TNF alpha, IL-4 and TGF-beta. Copaxone treatment was found to lead to a significant reduction in the mean annual relapse rate (from 1.4 prior to treatment to 0.6 during treatment) and stabilization of disability in 90% of the patients. The treatment was accompanied by an elevation of serum IL-10 levels, suppression of the pro-inflammatory cytokine TNF alpha mRNA, and an elevation of the anti-inflammatory cytokines TGF-beta and IL-4 mRNAs in PBLs. These results suggest that the beneficial clinical effects of Copaxone in MS patients may be attributed to changes in activation of T cell subsets and a shift from Th1 to Th2/Th3 cytokine profile, probably leading to Cop-1-driven mechanisms of bystander suppression.
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PMID:Treatment of multiple sclerosis with copolymer-1 (Copaxone): implicating mechanisms of Th1 to Th2/Th3 immune-deviation. 991 86

Interleukin 15 (IL-15) is a 14-15 kDa polypeptide that belongs to the 4 alpha-helix-bundle family of cytokines and was originally discovered due to its T cell proliferative activity. It utilizes the signal-transducing beta/gamma polypeptides of the IL-2 receptor complex, thus sharing many biological activities with IL-2, in addition to its high-affinity private receptor subunit IL-15R alpha. Accumulating evidence indicates that the biological relevance of IL-15 may not solely be confined to T lymphocytes, but to a variety of cell populations within the immune system as well as outside the immune system of the host. The expression of both IL-15 and its high-affinity receptor component, IL-15R alpha, are readily demonstrable in a wide variety of tissues and appear to be augmented in response to environmental/stress stimuli and infectious agents. There is increasing evidence to suggest that IL-15 may play an important role in protective immune responses, allograft rejection and the pathogenesis of autoimmune diseases, where mononuclear cell infiltration is a hallmark feature. Herein, the effects of IL-15 on cells associated with host defense, immunity and inflammation are reviewed and support a central role for this cytokine in orchestrating multiple aspects of effector functions in immunity and inflammation.
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PMID:Interleukin 15: its role in inflammation and immunity. 1119 99


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