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)

The aim of the investigation was to study directly the IL-2 receptor (IL-2R) and its subunits, p55 and p75 chains, either membrane-bound or soluble, on PBMC of patients with solid malignancies and, indirectly, the same patients' PBMC ability to produce IL-2. Fifty-eight cancer patients, 29 men and 29 women, were studied: their mean age was 57.3 yr, range 35-79. Twenty-two healthy age-sex-matched subjects served as controls. The tumors were the most common and the most representative among human cancers, i.e., breast, lung, head and neck, digestive tract and liver, prostate and gynecologic cancers: they were generally in advanced stages and in 23 cases metastatic. The PBMC proliferative response to PHA, PHA plus IL-2, and IL-2 was evaluated along with the response to PHA in the presence of anti-p55, anti-p75 monoclonal antibodies, or both. Moreover, membrane-bound IL-2R (p55 and p75 chains) on PHA-stimulated PBMC was detected, along with soluble IL-2R in the serum and in the culture supernatants. The conclusions suggest that in solid malignancies: the membrane-bound IL-2Rs, both p55 and p75 chains, are expressed normally, there is an high serum level of soluble IL-2R, there is a normal release of soluble IL-2R in culture, and there is an indirect evidence of a lack of IL-2 production. Therefore, no primary impairment of IL-2R was found in solid tumors. Moreover, in our study we have found no difference in any parameter studied between patients with and patients without metastases.
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PMID:Membrane-bound and soluble IL-2 receptors (p55 and p75 chains) on peripheral blood mononuclear cells from patients with solid malignancies. 788 44

Major adhesion routes between lymphoid cells involve the receptor/ligand pairs LFA-1/ICAM-1 and CD2/LFA-3, in addition to VLA or CD44 molecules. In this study we evaluated the role of these adhesion receptors in the proliferative response of lymphoid cells to interleukin-2 (IL-2). Blocking studies were performed with a panel of monoclonal antibodies (mAb) directed against these adhesion molecules. Selective inhibition of recombinant (r)IL-2-induced cell proliferation was observed with mAb directed against the alpha or beta subunit of LFA-1 or to its ligand ICAM-1. Interestingly, rIL-2-induced proliferation was also inhibited by NKI-L16, and anti-1 alpha antibody known to enhance cell-cell interaction. Resting lymphocytes were preferentially susceptible to the inhibition, particularly in an early phase of culture and when stimulated with a relatively low dose of rIL-2. By using mAb that specifically could block distinct rIL-2 activation pathways, LFA-1/ICAM-1 interaction was found to be required for p55 IL-2 receptor (IL-2R)-mediated interaction of rIL-2 with its high-affinity receptor, but not for p75 IL-2R-mediated responses. Furthermore, it was shown that the rIL-2 response of T lymphocytes, but not of natural killer cells, was dependent on LFA-1/ICAM-1 interaction. This suggests that LFA-1/ICAM-1 interaction is required for an optimal rIL-2 response of cells capable of IL-2 secretion. Our data provide evidence for the hypothesis that adhesion receptor-directed release of IL-2 may result in a locally high concentration of IL-2 that triggers high-affinity IL-2R signaling and up-regulates p55 IL-2R to enhance cytokine responsiveness.
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PMID:Role of LFA-1/ICAM-1 in interleukin-2-stimulated lymphocyte proliferation. 790 74

Ubenimex is used for the immunotherapy of malignant diseases as a biological response modifier (BRM) and shows beneficial effects as an adjuvant treatment. In the present study, the in vitro effects of ubenimex on the cytotoxic activity of peripheral blood lymphocytes (PBL) and spleen cells of cancer patients and the mechanism of killer cell activation were investigated. Cytotoxic activity against K562, KATO-III and autologous tumor cells was augmented by in vitro sensitization with ubenimex (p < 0.05). The optimal concentration of ubenimex for induction of cytotoxic activity was 1 micrograms/ml, similar to serum levels after clinical oral administration. The major population of killer cells activated by ubenimex recognizing K562 was CD16+, and those recognizing KATO-III were mainly CDA+ or CD8(5) cels and CD16+ NK cells, while CDA5 or CD8+T cells comprised the majority of killer cells which showed autologous tumor-killing activity. Augmentation of the cytotoxic activity of mononuclear cells by ubenimex was blocked by both anti-IL-1 beta Ab and anti-IL-2 AB. However, the expression of IL-2 receptor (p55, p75) on effector cells was not altered. Ubenimex augmented not only NK activity but also autologous tumor killing activity of PBL and spleen cells via macrophage activation. These activities of ubenimex may be clinically beneficial as an adjuvant treatment.
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PMID:In vitro augmentation of cytotoxic activity of peripheral blood lymphocytes and spleen cells of cancer patients by ubenimex. 797 85

Exact mechanisms of Mf and CsA effect have been investigated in BALB/c, DBA/2, CC57BR, and C57BL/6 mice. Different sensitivity of spleen cells of mice of different strains to Mf and CsA antiproliferative effect has been demonstrated. These interstrain variations have not been related with an inhibition of interleukin-2 (IL-2) release but, perhaps depended on the IL-2 receptor (IL-2R) expression differences. The p75 chain of IL-2R as a possible target for Mf, has been discussed.
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PMID:[Comparative study of mechanisms of antiproliferative action of low concentrations of mafosfamide and cyclosporin A]. 804 39

Expression of p55 and p75 chains of IL-2 receptor (IL-2R) on the surface of both T and natural killer (NK) circulating lymphocytes was investigated in 14 paediatric patients given allogeneic bone marrow transplantation (BMT) from HLA-identical sibling or partially matched family donors. IL-2-induced proliferative and cytotoxic responses were also studied and all analysis was performed within 45 days from transplant. We found that, early after transplant, the percentage of p55+ and of p75+ peripheral blood lymphocytes (PBL) was not significantly different in patients who had received HLA-identical BMT (p55+ 8.04 +/- 4.87%; p75+ 28.27 +/- 18.85%) compared with healthy controls (p55+ 7.26 +/- 6.17%; p75+ 19.42 +/- 10.49%), while recipients of T cell-depleted marrow included a remarkably high percentage (76-90%) of p75+ PBL, which were mostly CD3- and co-expressed CD56 molecule. Comparable values of p55+ lymphocytes were observed in all patients and controls. However, in contrast to the other two groups, in recipients of T cell-depleted BMT the majority of these cells co-expressed p75 chain and CD56 antigen. IL-2-induced proliferation and lymphokine-activated killer (LAK) activity were detectable in all patients, and their values did not correlate with expression of p55 or p75 chains. Our data suggest that expansion of NK subsets expressing IL-2R chains after T cell-depleted BMT may be related to early reconstitution of natural immunity in the presence of allogeneic stimuli.
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PMID:Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation. 808 8

DAB486IL-2 is an IL-2-diphtheria toxin conjugate which was developed to be specifically cytotoxic to cells bearing high affinity IL-2 receptors. The high affinity IL-2 receptor is a heterodimer comprising p55 and p75 subunits. While the p75 subunit appears to be ubiquitously expressed among the common North American leukemias and lymphomas, the p55 subunit is more restricted in its expression. To broaden the therapeutic relevance of the DAB486IL-2 we have sought physiologically feasible inducers of the p55 IL-2 receptor subunit. This report describes that PHA, in vitro, induces the p55 IL-2 receptor subunit on initially p55-negative B-CLL cells and converts toxin-insensitive leukemia cells to a toxin-sensitive state.
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PMID:PHA induces IL-2 receptors on B-CLL cells and is a potential biological response modifier for the LIL-2-diphtheria toxin, DAB486IL-2. 810 88

Using enzyme-linked immunoabsorbent assays for the soluble tumor necrosis factor (TNF) receptors type I (p55) and type II (p75) and IL-2 receptor we determined their levels in the plasma of 378 patients with various solid carcinomas, 56 patients with benign tumors, and 241 healthy controls. The plasma concentrations of both TNF receptors as well as the IL-2 receptor were significantly higher in the cancer patients than in the healthy controls, independent of the origin or histology of the tumor. The incidence and the extent of the receptor increase correlated with the extent of the disease. In the patients with benign tumors plasma levels of TNF receptor p75 and IL-2 receptor were not significantly different from the controls.
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PMID:Increased plasma concentrations for type I and II tumor necrosis factor receptors and IL-2 receptors in cancer patients. 814 26

The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector: target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10(-4) M beta-mercaptoethanol and 10(-6) M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1 alpha, IL-6, TNF-alpha, IFN-alpha, IFN-gamma) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28, CD45, CD54, CD56bright; surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor beta and gamma genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
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PMID:Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. 815 60

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

We investigated the immunological character of mononuclear cells obtained from the decidua in the first trimester of normal pregnancy. These cells showed in vitro cytotoxicity against NK cell targets, although with lower activity than that of the peripheral blood mononuclear cells. Response to IL-2 was dose-dependent. Since decidual CD56-positive cells express two IL-2 receptor subunits, p55 and p75, it is concluded that these cells have high-affinity receptors to IL-2. Peripheral blood CD56-positive cells, which express p75 alone, might have intermediate-affinity IL-2 receptors. These results indicate that the decidual mononuclear cells have a function resembling that of the peripheral blood NK cells in vitro, moreover, that even low levels of IL-2 can affect the character of the decidual mononuclear cells through the high-affinity IL-2 receptor. It is considered that the NK activity of decidual mononuclear cells is suppressed in conditions of low IL-2 levels to permit the maintenance of pregnancy, but can be rapidly elicited by intrauterine infections or abortion, both of which elicit the secretion of IL-2.
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PMID:Immunological characterization of human decidual mononuclear cells: natural killer activity, response to interleukin-2 and distribution of interleukin-2 receptor subunits. 817 20


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