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

EL 4-6.1 cells, variants of the murine EL4 thymoma cell line, can be activated by interleukin 1 (IL-1) or phorbol 12-myristate-13-acetate (PMA), or PMA+IL-1 to secrete interleukin 2 (IL-2) and interleukin 4 (IL-4) and to express the IL-2 receptor (IL-2R). To compare the different activation pathways, we examined the effects of staurosporine (STAR) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), two protein kinase C (PKC) inhibitors, on the induction of interleukin secretion and IL-2R expression in these cells. We report here that nanomolar concentrations of STAR strongly potentiated (20- to 30-fold) the production of IL-2 or IL-4, when EL 4-6.1 cells were induced by IL-1 alpha (or IL-1 beta) alone. By contrast, at identical concentrations, STAR dose-dependently inhibited the production of IL-2 and IL-4 resulting from PMA or PMA+IL-1 cell treatment. STAR also negatively affected the expression of IL-2R, which was dependent on PMA-sensitive PKC with either IL-1, PMA, or PMA+IL-1 stimulation. The changes in interleukin production and IL-2R expression in EL 4-6.1 activated cells were correlated with changes at the mRNA level measured by quantitative polymerase chain reaction (PCR). This finding suggests a pretranslational effect of the drug. At micromolar concentrations, H7 showed the same effects as STAR, but only increased IL-1-triggered interleukin secretions twofold. We observed that the action of PKC inhibitors did not result from modification of IL-1 receptor (IL-1R) expression in EL 4-6.1 cells. Thus, our data show that PKC inhibitors clearly distinguish between IL-1 and PMA stimulatory pathways. In addition, they suggest that the IL-1 stimulatory pathway involves PKC(s) [or other undefined kinase(s)] which regulate this pathway and differ from PKC(s) activated by PMA.
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PMID:Contrasting effects of the protein kinase C inhibitor staurosporine on the interleukin-1 and phorbol ester activation pathways in the EL4-6.1 thymoma cell line. 156 50

The aim of this study was to examine whether the unresponsiveness of MHC class I-negative subclones of the EL4 thymoma to CD3 cross-linking can be restored by transfection of class I genes into the H-2-negative cells. Cell activation experiments with selected MHC class I-negative subclones and H-2b- and H-2Ld-positive transfectants showed that these cells are equally capable of secreting interleukin 2 (IL-2) after exposure to the phorbol ester phorbol 12-myristate 13-acetate (PMA) and ionomycin. In contrast, only the parental H-2-positive EL4 cells are capable of responding to treatment with immobilized anti-CD3 antibody with IL-2 secretion and IL-2 receptor expression. Measurements of intracellular free Ca2+ (Ca2+i) following anti-CD3 antibody-induced cross-linking of parental EL4 cells and H-2-negative and H-2b gene-transfected subclones showed that the parental cells and two of the class I transfectants, one H-2-positive and one H-2-negative, responded with a slow rise in Ca2+i, whereas one H-2-positive transfected cell clone was completely refractory to CD3 cross-linking. Modulation experiments using parental EL4 cells, H-2-negative subclones and H-2-positive transfectants demonstrated that the CD3 and class I molecules of these different cells are modulated to the same extent after exposure to specific antibodies. The present findings thus indicate that the unresponsiveness of H-2-negative EL4 subclone cells to CD3 cross-linking is not functionally associated with a lack of class I surface expression.
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PMID:T-cell activation. III. Attempts to activate MHC class I-negative and class I-transfected EL4 T-lymphoma cells by immobilized anti-CD3 antibody. 214 10

Tumor cells of all types and species tested have been found to produce, in culture, substances that depress the expression of cell-mediated immunity, in the form of delayed-type hypersensitivity reactions in mouse feet. The factors responsible appear related immunologically to the retroviral envelope protein p15E. We have measured the effects of tumor products and conjugates of a p15E-related peptide, CKS-17, on interleukin-2 (IL-2) production by cultured, mitogen-stimulated EL4 cells; in this system IL-2 production is independent of IL-1. Supernatants of cultures of mouse, human and guinea-pig tumor cells inhibited IL-2 production in a dose-dependent fashion. CKS-17 conjugates, but not control conjugates, also inhibited IL-2 production. Responses to IL-2 of the CTLL line used were less inhibited by tumor products and very slightly inhibited by CKS-17 conjugates. IL-2 receptor density, assayed by flow cytometry, was not inhibited. IL-2 production was inhibited whether the tumor products or CKS-17 conjugates were added early or late in the course of culture of stimulated EL4 cells. Inhibition by CKS-17 conjugates was selective in that IL-2 production was inhibited to a greater degree than general protein synthesis in EL4 cells, and general protein synthesis by fibroblasts was unaffected. Measurement of IL-2 mRNA suggested that inhibition of IL-2 production was mediated post-transcriptionally. Fractionation of six different tumor supernatants on Sephacryl S-300 revealed a single peak of activity with an apparent molecular mass of 18 kDa. Antibodies to CKS-17 conjugates neutralized the inhibitory effect of native tumor products on IL-2 production. Inhibition of IL-2 production, by factors related to p15E, provides a strategically effective means of subversion of host defenses by tumors, and abrogation of this inhibition by means of antibodies might promote host resistance to tumor growth.
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PMID:Inhibition of interleukin-2 production by tumor cell products and by CKS-17, a synthetic retroviral envelope peptide. 230 24

This paper examines the possibility of a functional linkage between class I MHC molecules and the T-cell receptor complex for antigen (T3-Ti). A newly developed anti-CD3 antibody (500A2) was used as an activation signal for EL4 lymphoma cells and allospecific cytotoxic T-cell clones (CTL), and the production of IL-2/IL-2 receptor in EL4 cells and serine esterase in CTL was determined. Anti-CD3 antibody-induced activation of both EL4 and CTL cells was enhanced in the presence of immunologically cross-linked and immobilized anti-H-2 (class I) antibody reactive against the H-2 haplotype of the responding T cells. A number of H-2-negative and H-2-positive EL4 subclones were generated and tested for anti-CD3 antibody-induced IL-2/IL-2 receptor production. Although both H-2-positive and -negative subclones expressed CD3 antigen and produced IL-2 after activation with the phorbol ester TPA, only the H-2-positive cell clones produced IL-2 and expressed IL-2 receptor after anti-CD3 antibody induction. Our results are compatible with the existence of a functional linkage between the class I and the CD3 molecules on the surface of T cells.
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PMID:T-cell activation. I. Evidence for a functional linkage between class I MHC antigens and the Tc-Ti complex. 252 6

In a previous paper [Horuk, Huang, Covington & Newton (1987) J. Biol. Chem. 262, 16275-16278] we reported that there were fundamental differences in the biochemical properties of the interleukin-1 (IL-1) receptor between Raji and EL4 cell lines. In the present study we have investigated the basis for these differences. Kinetic studies measuring the on and off rates of IL-1 receptor binding revealed that the low-affinity IL-1-binding sites observed in Raji cells, compared with EL4 cells, result from a combination of a lower association rate and a higher dissociation rate in the Raji cells. The turnover of the Raji IL-1 receptor, measured by inhibiting protein synthesis with cycloheximide, was much faster than that of the EL4 IL-1 receptor, with a half-time of 2 h as against 5 h. Treatment of 125I-IL-1-labelled IL-1 receptors in Raji and EL4 cells with neuraminidase decreased their molecular mass by approx. 2-5 kDa as assessed by SDS/polyacrylamide-gel electrophoresis (PAGE). The covalently labelled IL-1 receptors in both cell types were sensitive to treatment with endoglycosidase F, which decreased their molecular mass on SDS/PAGE by 12-13 kDa. Incubation of Raji cells with maximally stimulating doses of IL-1 resulted in an increase in the nascent RNA levels of several genes, including the IL-2 receptor and the proto-oncogenes c-Ha-ras and c-myc.
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PMID:The interleukin-1 receptor in Raji human B-lymphoma cells. Molecular characterization and evidence for receptor-mediated activation of gene expression. 252 95

The cytokine interleukin-1 plays an important role in the induction of IL-2 secretion and IL-2 receptor expression. The events that follow binding of IL-1 to its receptor are not known. We found that in a purified T cell population (comprising the Lyt2- and L3T4- T cells) IL-1 in the absence of antigen or mitogen induced strong proliferation and de novo expression of IL-2R light chain mRNA. This was accompanied by high affinity IL-2 binding. Production of IL-2 or IL-2 mRNA was not detected under these conditions. As a model system for IL-1 action two EL4 subclones were isolated. EL4 5D3 responded to IL-1 by augmentation of PMA induced IL-2 secretion and IL-2R expression. EL4D6/76 bound IL-1 with the same affinity but did not respond. We found that this line was unable to internalize surface bound IL-1. The finding suggests that in T cells internalization of IL-1 is required for its activity.
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PMID:Activation of T cells by interleukin 1 involves internalization of interleukin 1. 278 20

Interleukin 2(IL-2), a lymphokine that is produced by helper T cells, plays a key role in the proliferation of T lymphocytes by interacting with a specific cell surface receptor. Recent studies demonstrated that the IL-2 receptor exists in two forms having different affinities to the ligand and the growth signal seems to be delivered by IL-2 bound to the high affinity, but not the low affinity, receptor. In man, both forms of the IL-2 receptor can be recognized by a monoclonal antibody, anti-Tac. Using this antibody, a cDNA that encodes Tac antigen has been cloned from ATL-derived T cell line. Transfection of the cloned cDNA into mammalian non-T cells, however, resulted in the expression of only a non-functional, low affinity IL-2 receptor. This observation raised a question whether or not the cloned cDNA for Tac antigen actually encodes the functional, high affinity IL-2 receptor. In order to clarify this problem, Tac antigen cDNA was obtained from human PBL cDNA library. This cDNA was connected to RSV-LTR and was transfected into mouse thymoma derived T-cell line EL4, and L929 fibroblast. Then transformants that constitutively express Tac antigen were established. IL-2 binding assay demonstrated that EL4 transformants expressed high affinity as well as low affinity human IL-2 receptor. In contrast, L929 transformants expressed only a low affinity receptor. The growth of the EL4 transformants harboring the high affinity human IL-2 receptor was inhibited by virtue of the specific interaction of the receptor with human, but not mouse, recombinant IL-2. These results demonstrate: the cloned cDNA dose encode a functional IL-2 receptor, the affinity of the IL-2 receptor is variably modified by post-translational events and 3. IL-2/receptor interaction leads to the reversal of the cell growth in EL4 cells. The reconstitution system described here will be of great use in elucidating the mechanism of T cell growth.
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PMID:[Expression of functional human interleukin 2 receptor in mouse cells by using gene transfection]. 309 55

Small, resting B lymphocytes express few, if any, interleukin 2 (IL-2) receptors, but activated B cells may express such receptors. This paper examines the requirements for receptor expression. Normal murine splenocyte populations were enriched for B cells and cultured at relatively low density. IL-2 receptor expression was studied by measuring the binding of the anti-IL-2 receptor monoclonal antibody PC61. Lymphoblasts arising through stimulation by Escherichia coli lipopolysaccharide failed to express IL-2 receptors. B cells cultured with conditioned medium from concanavalin A-stimulated EL4 thymoma cells, with or without LPS, displayed IL-2 receptors. This bioactivity of EL4 conditioned medium could not be replaced by any concentration of B-cell-stimulatory factor 1 (IL-4), IL-1, IL-2, or IL-3 tested. However, the recently cloned lymphokine T-cell-replacing factor (IL-5) was a potent inducer of IL-2 receptor expression, as was the probably identical material known as eosinophil differentiation factor. The receptors so induced appeared to be functional, as receptor-expressing (but not control) lymphoblasts, responded to IL-2 by proliferation, indicative of high-affinity-receptor expression.
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PMID:T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. 311 Jul 87

The murine interleukin 2 (IL-2) receptor is a 55- to 60-kDa glycoprotein (p58) that binds IL-2 at a high and low affinity. In this investigation, we have identified sublines of EL4 that vary in their capacity to express high affinity IL-2 receptors after transfection of the IL-2 receptor cDNA. These and other cell populations were used to determine whether unique membrane molecules were specifically associated with the high affinity IL-2 receptor. Irreversible chemical cross-linking of [125I]IL-2 to only high affinity IL-2 receptors resulted in detection of IL-2 cross-linked to p58 as a 70- to 75-kDa band and other complexes of 90 to 95 kDa, 115 kDa, 150 kDa, 170 to 190 kDa, and 245 kDa. Antibodies specific for p58 resulted in precipitation of each of these complexes. However, disruption of noncovalent interactions prior to immunoprecipitation resulted in an inability to detect the material at 90 to 95 kDa. Therefore, we conclude that this complex most likely represented IL-2 cross-linked to a 75- to 80-kDa subunit that was noncovalently associated with p58. The other complexes greater than 150 kDa may represent these subunits cross-linked to each other. The detection of all the cross-linked complexes larger than 75 kDa appeared to be directly related to formation of high affinity IL-2 receptors because IL-2 was cross-linked only to p58 for three cell lines that exclusively expressed low affinity IL-2 receptors. Thus, high affinity murine IL-2 receptors are comprised of at least one alpha (p58)- and beta (p75)-subunit. Our data also raise the possibility of a more complex subunit structure.
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PMID:The murine interleukin 2 receptor. Irreversible cross-linking of radiolabeled interleukin 2 to high affinity interleukin 2 receptors reveals a noncovalently associated subunit. 311 79

The thymocyte costimulator (LAF) assay, the standard biological test used for IL-1 titration, has a low sensitivity and lacks specificity since it can be potentiated by the IL-2 which is frequently present in IL-1-containing biological fluids. We describe here a new IL-1 titration method which takes advantage of the capacity of a thymoma line, EL4-6.1, to differentiate and express IL-2 receptors upon stimulation by IL-1 in the presence of a suboptimal dose of phorbol diester. Membrane IL-2R measurement on this indicator cell line permits the detection of 1-2 X 10(-4) ng/ml IL-1, compared to 5 X 10(-2) ng/ml in the LAF assay. In addition, rIL-2 up to 250 U/ml has no effect on IL-1 measurement by this assay, which also exhibits a 100-fold lower sensitivity to inhibitory effects of prostaglandin, compared to the LAF assay. Finally, tumor necrosis factor alpha only exerts a weak costimulation effect at very high doses. A flow cytometry technique and an ELISA are described for IL-2 receptor detection. Due to its high sensitivity and specificity, this novel assay should now permit reliable IL-1 titration in biological fluids such as IL-2-rich lymphocyte culture supernatants.
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PMID:A sensitive, IL-2-independent, assay for IL-1. 312 57


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