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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 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

Interleukin 2 (IL-2) binds to its receptors with three distinct affinities, with Kd values of 10(-11) M (high), 10(-9) M (intermediate) and 10(-8) M (low). IL-2 responding cells express two proteins that bind IL-2, i.e. a 55 x 10(3) Mr protein (p55 or L chain), which has classically been known as the IL-2 receptor and a second 75 x 10(3) Mr chain (p75 or H chain) with intermediate affinity. Experiments were performed to clarify the mechanism of the high-affinity site formation. Crosslinking of human IL-2 with the high-affinity sites of human T lymphocytes yielded a 150 x 10(3) Mr ternary complex consisting of IL-2, L and H chains. The ternary complex with human IL-2 was formed on EL/Tac 3 cells expressing human L and murine H chains, although human IL-2 was unable to bind to the parental EL-4 cell, which does not express human L chain. The high-affinity ternary complex was stable during solubilization and fractionated by gel-filtration chromatography, and the numbers of these complexes were quantified by this method. The number of high-affinity sites on the CT/hR-1 cells, which express the human L, murine L and murine H chains, was almost constant even when either the human or murine L chain was blocked by specific antibodies in agreement with a previous observation. These results indicate that the L and H chains do not form a stable binary complex by themselves and that IL-2 binding induces the formation of the stable high-affinity ternary complex.
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PMID:Molecular mechanism for the formation of the high-affinity complex of interleukin 2 and its receptor. 313 61

Previous studies have demonstrated that interaction of interleukin-2 (IL-2) with the beta chain (p75) of the IL-2 receptor on CD56+ cells is necessary for the development of lymphokine-activated killer (LAK) activity and proliferation of CD56+ LAK cells in response to IL-2. Human pulmonary macrophages (PM) are potent inhibitors of LAK cells in vitro, and purified resident human lung lymphocytes show limited LAK activity in response to IL-2, suggesting that IL-2-p75 interactions may be altered locally in vivo. In the current study, human PM or anti-p75 inhibited LAK activity and proliferation of CD56+ cells in response to IL-2. This effect was produced by either live or paraformaldehyde-fixed PM, but not peripheral blood monocytes, suggesting that a membrane signal on PM was responsible for inhibition. Suppression of LAK function and proliferation in response to IL-2 occurred despite a rapid up-regulation of p75 on CD56+ cells after 24 h of incubation with PM. Greater than 70% of CD56+ cells expressed p75 after culture with either live or fixed PM, compared with 10 to 15% at 0 h or after 24 h of incubation in IL-2 alone. p75 dim and p75 bright cells increased equally, suggesting that p75 was being up-regulated on previously p75- cells rather than an overexpansion of one subset of p75+ cells. The increase in p75 expression in the presence of PM paralleled with an increase in IL-2 binding to these lymphocytes. These results suggest that PM inhibit the activation of LAK cells at a point distal to IL-2-p75 binding.
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PMID:Inhibition of lymphokine-activated killer cells by human pulmonary macrophages: discordance between up-regulation of the beta chain (p75) of the interleukin-2 receptor on CD56+ cells and limited response to interleukin-2. 750 62

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.
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PMID:Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. 752 71

Ten patients with high-grade non-Hodgkin's lymphoma (HG-NHL) entered a subcutaneous (s.c.) recombinant interleukin 2 (rIL2) trial within 2 months of undergoing autologous bone marrow transplantation (ABMT). Immunological studies, consisting in T- and natural killer (NK)-cell subset assessment, together with functional assays, such as NK activity and CD16-mediated redirected killing assay, were performed before therapy, after 2 weeks, and then monthly. Phenotypic analysis showed a significant increase (p = 0.01) of CD16 and CD56 NK cells, from 12% to 28% and from 17% to 37%, respectively. In particular, the CD56bright NK cell population showed a tenfold increase, while CD56dim NK cells remained unmodified compared with pretreatment values. The expression of IL2 receptors was also studied and a significant increase (p = 0.01) of CD122 (p75)-positive cells from 8% to 30% was found, while no significant increase was observed in CD25 (p55)-positive cells. Furthermore, rIL2 administration led to an increase of NK activity even at the lowest effectors:target ratio and to an increase of CD16-mediated redirected killing assay. These phenotypic and functional modifications lasted throughout the duration of rIL2 therapy and remained after completion of therapy. In addition, none of the ten patients relapsed, and two of them who started IL2 treatment while still showing residual disease experienced a complete disappearance of the disease after 10 and 7 months of therapy, respectively. Our data suggest that infusion of rIL2 s.c. after ABMT is safe, can selectively increase NK cell number and function, and may have a beneficial effect on the minimal residual disease.
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PMID:Low doses of rIL2 after autologous bone marrow transplantation induce a "prolonged" immunostimulation of NK compartment in high-grade non-Hodgkin's lymphomas. 757 23

Ouabain, a specific inhibitor of the Na-K ATPase, has been shown to exert immunosuppressive effects. The goals of this study were to define the stage of the proliferative response which is sensitive to ouabain and to correlate the inhibitory action of ouabain on cell proliferation with its effect on Na-K ATPase activity. We found that ouabain inhibited T-cell proliferation in a dose-dependent manner and this inhibition was similar in CD4+ and CD8+ T cells. To define the role of the Na-K ATPase in early activation of T lymphocytes, we examined the effects of ouabain on the induction of competence (acquisition of responsiveness to interleukin (IL)-2 or IL-4) by phytohemagglutinin (PHA) or the combination of phorbol dibutyrate/ionomycin. Ouabain, at concentrations that completely inhibited the enzyme activity, did not interfere with the induction of competence, suggesting that although activated cells express increased activity of Na-K ATPase, this enzyme activity does not play a role in early activation pathways. In contrast, ouabain inhibited the progression phase to DNA synthesis in a dose-dependent manner even at concentrations that had little or no effect on Na-K ATPase activity. This inhibition was not due to a decrease in the production of IL-2 but rather to an inhibition of the expression of the p55 and p75 subunits of the IL-2 receptor (IL-2R). The inhibition of p55 appeared to occur at the mRNA level. These results indicate that the activity of the Na-K ATPase is not essential for the induction of competence or early activation. On the other hand, inhibition of cell proliferation and transcription of IL-2R subunits by low concentrations of ouabain may be related to changes in intracellular K+ concentrations or to inhibition of membranal phospholipid metabolism secondary to alteration in Na-K ATPase activity.
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PMID:Ouabain induces inhibition of the progression phase in human T-cell proliferation. 759 2

The intravenous injection of mice with lymphocytic choriomeningitis virus (LCMV) induces a rapid and long-lasting immunodeficiency. T lymphocytes from 7-day-infected mice do not proliferate in vitro in response to ConA stimulation, do not produce IL-2 but display high affinity IL-2 receptors on their membrane. The non-coordinated regulation of these genes suggested that other cytokine-encoding genes may also be affected in their regulation. We have thus analyzed the expression of the genes encoding different cytokines transcribed during spleen cell activation by ConA. The genes encoding T lymphocyte-derived cytokines can be classified in three groups: the genes expressed similarly by normal and LCMV-cells (the p55 and the p75 chains of the IL-2 receptor [1]), the genes under expressed in LCMV-cells (IL-2, IL-3, IL-4 and IL-5) and the genes over expressed by these cells (GM-CSF and IFN-gamma). These results show that the viral infection has provoked a profound alteration of the overall regulation of the genetic program that follows T lymphocyte activation. Since T cell activation depends strictly on accessory cell-derived cytokines, we measured the level of transcription of IL-1, IL-6 and TNF-alpha; and our data show that the expression of these genes is equivalent in normal cells and in cells from LCMV-infected mice.
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PMID:Altered cytokine genes expression by conA-activated spleen cells from mice infected by lymphocytic choriomeningitis virus. 768 35

By using high-sensitivity fluorescence and flow cytometry, it is possible to show that 30-40% of lymphocytes from PBL express the p55 chain of the IL-2 receptor, whereas the p75 chain is expressed at low concentrations on most lymphocytes without in vitro activation. The availability of a second fluorochrome capable of high sensitivity allows simultaneous analysis of p55 and p75, albeit with some sacrifice in sensitivity. Two-color analysis shows that a small proportion of cells (1-6%) coexpress measurable concentrations of both chains of the IL-2 receptor, and three-color studies show that these cells are predominantly CD4-positive T cells and express the CD45R0 isoform of the leucocyte-common antigen, i.e., have the phenotype of activated helper T cells. These cells may be a useful indicator of immune activation.
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PMID:Coexpression of IL-2 receptor p55 and p75 by circulating blood lymphocytes. 768 29

Interleukin-2 (IL-2)-induced generation of non-major histocompatibility complex (MHC)-restricted killer cells among human cord blood lymphocytes (CBL) was investigated. After 1 week in culture with recombinant (r)IL-2 and human serum (HuSer), the cytotoxicity of CBL against K562 and COLO cells greatly exceeded the cytotoxicity of cultured adult peripheral blood lymphocytes. Culturing of CBL with rIL-2 and HuSer led to preferable generation of CD56+ cells. After 1 month in culture, the number and frequency of CD56+ cells had increased by more than 50 and nine times, respectively. The generation of CD56+ cells in CBL cultures may at least partially be explained by their comparatively strong expression of the IL-2 receptor (IL-2R) beta-chain (p75).
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PMID:Non-major histocompatibility complex-restricted killer cells in human cord blood: generation and cytotoxic activity in recombinant interleukin-2-supplemented cultures. 769 29

Immunophenotyping by dual parameter flow cytometry was used to compare the expression of interleukin-2 receptor alpha and beta chains on lymphocyte subsets in the peripheral blood of 7 trained and 6 untrained volunteers (respective VO2max 57.0 +/- 6.1 and 39.0 +/- 4.5 ml.kg-1.min-1). Venous blood samples were collected at least 36 h after the most recent exercise session. The trained subjects had higher circulating counts (10(9).l-1) of total leukocytes (5.80 +/- 0.83 vs. 4.63 +/- 0.21, p < 0.05), granulocytes (3.14 +/- 0.72 vs. 1.90 +/- 0.30, p < 0.05), and NK cells (CD16+, 0.32 +/- 0.14 vs. 0.16 +/- 0.05, p < 0.05; CD56+, 0.41 +/- 0.14 vs. 0.21 +/- 0.03, p < 0.01), but lower lymphocyte counts than their sedentary peers (1.90 +/- 0.22 vs. 2.26 +/- 0.25, p < 0.05). Counts for T cells (CD3+) and B cells (CD19+), and the CD4+/CD8+ ratio did not differ between the two subject groups. The p55-IL-2 receptor alpha expression (CD25+: 0.63 +/- 0.11 vs. 0.69 +/- 0.17) was unrelated to training, but the p70-75-IL-2 receptor beta expression was higher in the active group (p70/Mik-beta 1+: 0.42 +/- 0.09 vs. 0.20 +/- 0.06, p < 0.001; p75/TU27+: 0.36 +/- 0.08 vs. 0.17 +/- 0.07, p < 0.005). Beta chain co-expression was also higher on NK cell subsets (p < 0.001) in trained than in sedentary subjects. Aerobic power was strongly correlated with IL-2R beta expression (r = 0.914, p < 0.001 for Mik-beta 1; r = 0.884, p < 0.005 for TU27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expression of interleukin-2 receptor alpha and beta chains in relation to natural killer cell subsets and aerobic fitness. 782 69


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