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

The binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) on human T-cells is a key regulatory event which is absolutely required for T-cell-mediated immune responses. To understand further this binding event, we modified the human IL-2R gene to encode a secreted form of IL-2R. Secreted IL-2R was then expressed at very high levels (approximately 11 micrograms/10(6) cells/48 h) in rodent cells using gene-linked co-amplification. The soluble forms of IL-2R were shown to retain IL-2 affinity shown by cell-surface IL-2R (Kd approximately 18 nM) and were purified to homogeneity using IL-2 affinity chromatography. Purified, recombinant IL-2R and biotinylated IL-2 were used to establish a solid-phase receptor binding assay. Binding of IL-2-biotin was demonstrated to be dose-dependent at concentrations ranging from 10 to 1000 ng/ml, and the specificity of receptor-ligand binding was demonstrated by competition with non-biotinylated IL-2 and with anti-receptor antibodies known to block IL-2 binding in vivo. This immunosorbent receptor assay offers a simple and rapid method for studying the binding of IL-2 to human IL-2R.
J Biol Chem 1987 Dec 25
PMID:Biochemical and functional analysis of soluble human interleukin-2 receptor produced in rodent cells. Solid-phase reconstitution of a receptor-ligand binding reaction. 312 94

Peripheral blood mononuclear cells (PBMC) of normal individuals were found to contain a proportion (4-9%) of in vivo activated lymphoid cells (IVALC). These IVALC were characterized by their expression of interleukin 2 (IL-2) receptors, and by the ability to proliferate in the presence of exogenous IL-2. There was a good correlation between the proportion of IVALC in different cell populations and the level of cell proliferation to IL-2. It was found that IVALC isolated from autologous PBMC of Bacillus Calmette-Guerin (BCG)-immunized individuals contained no significant proportion of purified protein derivative (PPD)-reactive lymphocytes. The addition of IVALC markedly enhanced proliferative responses of the autologous T4+T8-IL-2 receptor-negative cell cultures to antigen stimulation. An increased proportion of activated (IL-2 receptor-positive) lymphocytes was generated in PBMC as compared to autologous T4+T8-IL-2 receptor negative cell cultures after stimulation with PPD. Limiting dilution analysis showed that IL-2 responsive IVALC through expansion markedly affected the cloning efficiency of antigen-proliferating T cells of autologous PPD-stimulated PBMC cultures. Only 1 out of every 11-25 blast cells generated in the PBMC cultures could establish itself as a growing colony based on determinations in six BCG-positive individuals. By using a T4+T8- population depleted of IVALC to generate PPD-reactive lymphocytes, a three- to four-fold increase in the cloning efficiency of antigen-specific cells was obtained.
Scand J Immunol 1987 Dec
PMID:In vivo activated lymphoid cells (IVALC) affect the cloning efficiency of human T lymphocytes reactive to a soluble antigen, purified protein derivative. 312 12

DL-alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase [EC 4.1.1.17] (ODC), inhibited concanavalin A-induced proliferation of splenic mononuclear cells (SMNC). The inhibition was not reversed by interleukin-2 (IL-2) addition. Although DFMO did not affect the production of IL-2 or the expression of high-affinity IL-2 receptor, IL-2-dependent proliferation of SMNC was inhibited by DFMO, and the inhibition was reversed by exogenous putrescine. The inhibition of IL-2-dependent DNA synthesis appeared to be related to the decrease in intracellular polyamines. When the proliferation of SMNC was induced by IL-2, ODC activity was also increased. A similar result was obtained in the proliferation of an IL-2-dependent T cell line, CTLL. The time course of ODC induction was similar to that of IL-2 production by concanavalin A-stimulated SMNC. These results indicate that polyamine biosynthesis is necessary for IL-2-dependent proliferation, but not for IL-2 production or IL-2 receptor expression.
J Biochem 1987 Dec
PMID:Polyamine biosynthesis is necessary for interleukin-2-dependent proliferation but not for interleukin-2 production or high-affinity interleukin-2 receptor expression. 312 15

High levels of soluble IL-2 receptor (sIL-2R) are detectable in the serum of HCL patients. To determine the cell source of this molecule, we evaluated the presence of sIL-2R in the supernatants obtained from in vitro cultures of leukemic (hairy cell, HC) and non-leukemic lymphocytes from six untreated HCL patients and from an additional four patients under therapy with rIFN-alpha 2. We demonstrated that cultured HCs at resting conditions were able to spontaneously release the sIL-2R, whereas control enriched B cells did not. This phenomenon was present only when culturing HCs recovered from patients observed at the time of diagnosis but was not observed during treatment with rIFN-alpha 2. Following activation in vitro with a series of different stimulatory agents including BCGF, phorbol myristate acetate, and anti-human IgM antibody, cultured HCs increased their capability to shed the IL-2R molecules. On the other hand, the release of sIL-2R from enriched T cell populations from HCL patients did not significantly differ from the value obtained in controls. Taken together, these findings provide evidence that leukemic B cells represent the main source of sIL-2R in HCL patients and further emphasize the importance of evaluating this parameter as a relevant marker for monitoring the effectiveness of rIFN-alpha 2 therapy.
Leukemia 1988 Dec
PMID:Origin of the soluble interleukin-2 receptor in the serum of patients with hairy cell leukemia. 326 62

The present study was undertaken to assess the efficacy of recombinant Interleukin 2 (rIL-2: S-6820) in treatment of superficial bladder tumors. Three intratumor injections at a dose of 5 x 10(5) units/day via urethra, were performed every other day under endoscopic control in 12 patients with superficial bladder cancer. On the 15th day after completion of the series of injections, the tumor had disappeared in one patient and 50% regression over was observed in two other patients. Therefore, the response rate to the rIL-2 treatment in our study was 25.0%. Each tumor which responded to the therapy, was single, small and low grade. In the peripheral blood of the 12 patients, an increase in IL-2 receptor-positive lymphocytes and augmentation of natural killer activity were detected after the rIL-2 intratumor injection. There were no serious side effects except for moderate fever in our study.
Hinyokika Kiyo 1988 Dec
PMID:[The efficacy of recombinant interleukin 2 in local treatment of superficial bladder tumors]. 326 44

The effect of cyclosporine and metabolite 17 (M17) as well as other CsA-related compounds (CsG, dihydro-CsC, dihydro-CsD, CsH, B5.49, and H7.94) was tested on T lymphocyte clone proliferation. In these experiments, antigen and interleukin 2 (IL-2) dependent long-term T lymphocyte clones derived from a rejected human kidney graft infiltrate were used. They were specifically committed (proliferation and cytotoxicity) for the donor Epstein-Barr virus (EBV)-transformed cells. CsA strongly inhibited clone T cell proliferation induced by the antigen. Inhibition of antigen-driven proliferation was reversed by pure recombinant IL-2 (rec-IL-2) only when low amounts of CsA (less than 25 ng/ml) were used, whereas this lymphokine was ineffective at higher but still pharmacological CsA concentrations (50-500 ng/ml). Increasing rec-IL-2 concentrations did not modify this finding. In addition, CsA, did not inhibit the growth signal(s) induced by rec-IL-2/IL-2 receptor interactions when R-IL-2 is pre-expressed on clone cells. M17 was far less effective in inhibiting antigen-induced clone cell proliferation (50% inhibition at 16 ng/ml versus 500 ng/ml with, respectively, CsA and M17) but was nevertheless inhibitory. This observation, if extended to other metabolites, could be important for interpretation of the relevance of "CsA" concentration through radio-immunoassay monitoring of recipients' blood. Although CsA appeared to display the major inhibitory effect, dihydro-CsC and CsG, as well as B5.49 and H7.94 CsA-related compounds, also exhibited strong activity. Dihydro-CsD was less inhibitory, and CsH had no effect.
Transplantation 1987 Dec
PMID:Effect of cyclosporine, cyclosporine metabolite 17, and other cyclosporine-related compounds on T lymphocyte clones derived from rejected human kidney grafts. I. Inhibition of proliferation. 332 90

We have genetically replaced the diphtheria toxin receptor binding domain with a synthetic gene encoding interleukin-2 (IL-2) and a translational stop signal. The diphtheria toxin-related T-cell growth factor fusion gene encodes a 70 586-d polypeptide, pro-IL-2-toxin. The mature form of IL-2-toxin has a deduced mol. wt of 68,086 and is shown to be exported to the periplasmic compartment of Escherichia coli (pABI508), and contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. IL-2-toxin has been purified from periplasmic extracts of recombinant strains of E. coli (pABI508) by immunoaffinity chromatography using immobilized anti-IL-2. The purified chimeric toxin is shown to selectively inhibit protein synthesis in IL-2 receptor bearing targeted cells, whereas cell lines which do not express the IL-2 receptor are resistant to IL-2-toxin action.
Protein Eng 1987 Dec
PMID:Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein. 333 1

The expression of human cell-membrane antigens by hybrid cell lines derived by fusing a human B-ALL and mouse BW 5147 T-lymphoma cells has been studied. Using monoclonal antibodies (mAb), the phenotypes of 19 of the 24 hybrids which grew 11-44 days post-fusion have been analysed by indirect membrane immunofluorescence (IF). These uncloned hybrid cells were assayed early after outgrowth, prior to extensive human chromosome and antigen loss. Nonetheless, cytogenetic analysis showed that all hybrids contained variable numbers of human chromosomes. Phenotypic analysis showed that the hybrids could be grouped as follows: a high frequency expressing CD25 (IL-2 receptor), human T200, HLA class I alpha and beta 2microglobulin, and reacting with the mAb H207 and 12E7; an intermediate frequency expressing CD1 and CD2; and a low frequency expressing CD3, CD4, CD5, CD7, CD8 and CD9. This pattern of antigen expression resembled the frequency of these cells in the human B-ALL parent line. Cell sorting was used to immunoselect hybrids expressing CD1 and CD2, but CD1 expression was unstable during subsequent culture.
Immunology 1987 Dec
PMID:Expression of human CD antigens, including CD1 and CD25, by human x mouse interlineage leukaemia hybrids. 342 25

Four out of eighteen (22%) patients with nickel contact sensitivity showed inhibition of skin patch test responses to the allergen in the presence of topical cyclosporin A (CsA; 5% v/v). No systemic drug absorption or side effects were detected. The clinical response to CsA was accompanied by marked diminution of the T cell infiltrate, although no alteration in the helper/suppressor cell ratio was observed. Expression of the Leu 6 marker on epidermal Langerhans cells and of major histocompatibility complex (MHC) class II antigens (HLA-DR, DQ and DP) on lymphocytes and Langerhans cells was unaffected by topical CsA. The incidence of IL-2 receptor positive lymphocytes in all biopsies was too small to ascertain the influence, if any, of CsA. The prospective use and method of application of CsA in immune contact dermatitis and other immunologically-based skin disorders warrants further evaluation.
Clin Exp Immunol 1986 Dec
PMID:Topical cyclosporin A in nickel contact hypersensitivity: results of a preliminary clinical and immunohistochemical investigation. 355 35

We have studied the expression of seven cell cycle-dependent genes in phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells, in macrophage-depleted cultures and in macrophage-depleted cultures plus Interleukin-2 (IL-2). The expression of all seven genes is increased in PHA stimulated peripheral cells. Only two (2F1 and the IL-2 receptor) are increased in PHA-stimulated macrophage depleted cultures. Addition of IL-2 to these cultures increased the RNA levels of four genes (KC-1, c-myc, beta-actin and IL-2R), but has no effect on three others (4F1, 2F1, and JE-3). The results indicate that the expression of these cell cycle genes is regulated by different components of the mitogenic stimulus.
Biochem Biophys Res Commun 1985 Dec 17
PMID:Effect of interleukin-2 on the expression of cell cycle genes in human T lymphocytes. 387 9


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