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

Murine interleukin-2-dependent T-lymphocytes (CT6) were treated with tunicamycin, an inhibitor of both glycoprotein and ganglioside synthesis, to study the involvement of glycosylation in the IL-2 proliferative response. Tunicamycin inhibited proliferation in a dose-dependent manner at concentrations which did not inhibit protein synthesis (10-50 ng/ml). Swainsonine, a glycoprotein processing inhibitor, had no effect on proliferation. Inhibition of proliferation by tunicamycin was accompanied by an inhibition of binding of 125I-IL-2 to its high-affinity receptor. Scatchard analysis showed that receptor number was decreased by tunicamycin treatment. On the other hand, tunicamycin did not affect either the binding of the monoclonal antibody 7D4, specific for the 55 kDa low-affinity protein subunit of the IL-2 receptor, or the recycling of the IL-2 receptor. To determine the specific effects of tunicamycin on the biosynthesis of particular CT6 glycoconjugates, cells were radiolabeled with 3H-glucosamine and incorporation into ganglioside, neutral glycolipid and glycoprotein fractions was measured. Low doses of tunicamycin inhibited ganglioside synthesis and glycoprotein glycosylation to the same extent, whereas no effect on neutral glycolipid synthesis was observed. These results suggest that glycosylation of glycoprotein and/or gangliosides might play an important role in the formation of a functional high-affinity IL-2 receptor complex in CT6 cells.
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PMID:Tunicamycin inhibits function and expression of the high-affinity IL-2 receptor in a murine IL-2-dependent cell line. 152 26

The high-affinity cell-surface receptor for interleukin-2 (IL-2R) consists of the 75-kilodalton (kd) chain and a 55-kd glycoprotein known as Tac. This report examines the cellular expression of IL-2R and secretion of the soluble form of Tac in immunosuppressed blunt trauma (n = 20, injury severity score -20) and thermally injured (n = 20, Total body surface area greater than 35%) patients. The percentage of IL-2R-expressing peripheral blood mononuclear cells (PBMC) in mitogen-stimulated cultures from patients and age-matched normal donors was determined by direct immunofluorescence with a monoclonal anti-Tac followed by flow cytometry analysis. Levels of soluble Tac in patient sera were measured by a monoclonal antibody-based enzyme-linked immunosorbent assay. Expression of Tac antigen by mitogen-activated PBMC cultures from blunt trauma patients was transiently reduced (by as much as 40%) in 4 of 14 patients examined. Levels of serum Tac were significantly elevated (p less than 0.05) in 15 of 20 blunt trauma patients ranging from 750 to 3000 U/mL compared with 180 to 420 U/mL in control subjects. All burn patients studied 10 to 50 days after the injury demonstrated a significant reduction (by 50% to more than 90%) in the percentage of IL-2 receptor-bearing cells. Similarly serum levels of IL-2R increased significantly (p less than 0.001 to 0.05) in all burn patients studied, reaching concentrations as high as 5500 U/mL. These results suggest that major trauma, whether mechanical or thermal, induces alterations in the T-lymphocyte activation process. However the degree and duration of such changes may vary based on the nature of the injury.
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PMID:Expression and secretion of IL-2 receptor in trauma patients. 214 78

A panel of human T cell clones bearing exclusively the T4 (helper) phenotype and demonstrating specificity to a well-characterized soluble glycoprotein antigen (185,000 dalton streptococcal antigen, SA) is described. After having been cultured in exogenous interleukin 2 (IL-2) for 7 days in the absence of the specific antigen, two of the clones, namely SA1.4 and SA1.23, show stronger proliferative responses to the ligand as compared to the other T4 clones. Analysis of both the high- and low-affinity IL-2 receptor (IL-2R) levels reveals that IL-2 mediates differential regulation of high affinity IL-2R expression on these antigen-deprived cloned cells. Higher levels of surface expression of the IL-2 binding sites on SA1.4 and SA1.23 as compared to the other clones are observed throughout the 7-day culture period that these lymphocytes are maintained in exogenous IL-2. All the cloned cells appear to have returned to their "unstimulated states" as noted by their stable low expressions of Tac antigen and high affinity IL-2R. The unstimulated states of SA1.4 and SA1.23 are represented by higher levels of high affinity IL-2R expression. Under the condition in which the cloned cells are exposed to a decreasing concentration of IL-2, SA1.4 and SA1.23 are found to secrete a greater amount of IFN-gamma. The present results therefore suggest that a control mechanism involving the "mutual amplification" of IL-2 and IFN-gamma regulates the differential expression of high affinity IL-2R on antigen-specific T4 clones.
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PMID:Differential regulation of interleukin 2 (IL-2) receptor expression on antigen-specific human T cell clones by IL-2. 245 Aug 41

Interleukin 2 (IL-2) is a secreted glycoprotein which acts as an activation and proliferative signal for lymphocytes expressing membrane-bound glycoprotein IL-2 receptors. We have recently established that swainsonine (SW), an inhibitor of mannosidase II during N-linked glycoprotein processing, augmented mitogen-induced mononuclear leukocyte IL-2 receptor expression and IL-2-induced proliferation. The objective of the present investigation was to examine the effect of SW on lymphokine-activated killer (LAK) cell induction. Human mononuclear leukocytes were treated with various concentrations of SW (0.1-10 micrograms/ml) and IL-2 (1-100 units/ml) for up to 72 h. SW augmented IL-2-induced LAK activity directed against human lung carcinoma, melanoma, and leukemia cells 2-3-fold. LAK activity generated in the presence of SW at suboptimal doses of IL-2 (10 units/ml) was similar to that observed with higher concentrations of IL-2 (100 units/ml) alone. SW treatment alone or in combination with IL-2 increased the percentage of IL-2 receptor-positive cells. Furthermore, pretreatment with SW subsequently enhanced IL-2-induced lymphocyte proliferation. SW-treated mononuclear leukocytes exhibited an increase in high-mannose type glycoproteins based upon [3H]mannose labeling, susceptibility to alpha-mannosidase, and binding to concanavalin A-Sepharose. These results indicate that modulators of glycoprotein processing may be useful in lowering the concentrations of IL-2 required for LAK induction and maintenance.
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PMID:Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. 250 Oct 20

The leukocyte-common antigen (L-CA) is a family of large molecular weight glycoproteins uniquely expressed on the surface of all nucleated cells of hematopoietic origin. The glycoprotein consists of a heavily glycosylated exterior domain, a single membrane spanning region, and a large cytoplasmic domain that contains tyrosine phosphatase activity. To investigate the function of this family, we generated T cell clones that lacked L-CA (L-CA-). The expression of the alpha beta T cell receptor, CD3, CD4, IL-2 receptor (p55), LFA-1, Thy-1, and Pgp-1 (CD44) was normal. The L-CA- T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2. An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen.
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PMID:Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. 255 Jan 43

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90

CD4 (T4) is a 60 kD glycoprotein expressed on a subset of T lymphocytes. CD4 augments T cell responses to suboptimal Ag stimulation. In addition, the CD4 molecule is the receptor for HIV-1. CD4 is phosphorylated on serine residues within the cytoplasmic domain and its cell surface expression is decreased in response to PMA, APC bearing the appropriate Ag or HIV infection. The kinetics of CD4 phosphorylation and modulation are similar, suggesting that the two events may be related. L3T4, the murine CD4 equivalent, is not modulated from the surface of mature, peripheral T cells in response to PMA. The difference in the ability to modulate L3T4 and CD4 in response to PMA may be due to differences between the two molecules or to differences between the cells in which they are expressed. To further define the requirements for CD4 modulation, we used retroviral vectors to transfer the cDNA for CD4 and various mutants of CD4 into two murine T cell hybridomas that express L3T4. One of these hybridomas, By155.16, does not modulate L3T4 in response to PMA and the other, 5D5.63, does modulate L3T4 in response to PMA. When expressed by these hybridomas CD4 is not modulated from the surface of By155.16 and is modulated from the surface of 5D5.63 in response to PMA. In both of these hybridomas, CD4 is phosphorylated on serine residues in response to PMA. A mutant form of CD4, CD4 delta, was constructed in which the majority of the cytoplasmic domain was deleted. When expressed in 5D5.63, CD4 delta was not modulated in response to PMA. Replacing the cytoplasmic domain of CD4 with that of the human IL-2 receptor did not reconstitute the ability of CD4 to be modulated. These results suggest that the inability to modulate L3T4 from the surface of murine peripheral T cells is due to features of the cell and not the molecule. Furthermore, the cytoplasmic domain of CD4 is required for its modulation from the cell surface in response to PMA.
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PMID:Requirements for modulation of the CD4 molecule in response to phorbol myristate acetate. Role of the cytoplasmic domain. 278 43

The inhibitory effect of a diphtheria toxin-related interleukin 2 fusion protein, IL-2-toxin, on protein synthesis in adult T-cell leukemia/lymphoma (ATL) cells was examined in vitro. Peripheral blood ATL cells from 12 patients (six acute type, four chronic type, and two smoldering type ATL) and the lymph node cells from three ATL patients (two acute type and one lymphoma type ATL) were examined. At a concentration of 10(-8) M, IL-2-toxin inhibited protein synthesis by 60 to 98% in lymph node ATL cells, whereas protein synthesis in peripheral blood ATL cells was inhibited from 20 to 57% in acute type, and from 3 to 13% in chronic type. In contrast, IL-2-toxin had no measurable effect on T-cells from either patients with smoldering type ATL or normal controls. The cytopathic effects of IL-2-toxin were blocked by the addition of anti-CD25 monoclonal antibody, suggesting that the inhibition of protein synthesis in target cells was mediated by the IL-2 receptor (IL-2R). The degree of inhibition of protein synthesis, however, was not closely correlated with expression of CD25 antigen (low-affinity Mr 55,000 glycoprotein, IL-2R, Tac antigen) on ATL cells. There was an apparent correlation between the degree of inhibition and the rate of protein synthesis in ATL cells. We demonstrate that ATL cells from patients with acute or lymphoma type disease were more sensitive to IL-2-toxin than cells from chronic or smoldering disease. These findings suggest that the high affinity IL-2R present on acute and lymphoma type ATL cells may serve as a target for therapy with this recombinant chimeric toxin.
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PMID:Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia. 278 49

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62

An immunosuppressive factor was obtained from culture supernatants of early human decidual cells. The suppressor factor was concentrated by gel filtration in a fraction with a molecular weight between 43,000 and 67,000 daltons. It was further purified by biochemical methods. Four peaks were obtained in the fraction with molecular weight between 43,000 and 67,000 daltons by anion exchange chromatography. Only the second peak had immunosuppressive activity in MLR. Lentil-lectin affinity chromatography of this suppressor factor showed that the suppressor factor had no affinity for lentil-lectin sepharose. Isoelectric focusing of the suppressor factor demonstrated four bands. The protein isoelectric (PI) point was approximately 7.50 in one band and between 6.85 and 7.35 in the other three bands. These results demonstrate that the suppressor factor is not glycoprotein but protein, whose PI is between 6.85 and 7.50. The suppressive effect of this purified factor on lymphokine production and lymphocyte activation was investigated. The addition of the purified suppressor factor to a culture of PBL stimulated with PHA suppressed not only IL-2 production and gamma-INF production, but also BSF-2 production. IL-2 receptor expression and transferrin receptor expression of PBL stimulated with PHA were also suppressed by addition of the suppressor factor. These results demonstrate that this suppressor factor inhibits lymphokine production and lymphocyte activation.
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PMID:Immunochemical characterization of the suppressor factor from early human decidual cells. 279 18


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