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)

In this study, we have investigated the expression of the alpha and beta chains of the IL-2 receptor (IL-2R alpha, IL-2R beta) both at the membrane and at transcriptional levels during the lifespan of human embryonic fibroblasts. Here we show that the mAbs IOT14 and MIK beta 1 directed against the IL-2 binding sites of the IL-2R alpha and IL-2R beta respectively, stain human embryonic fibroblasts early in their life span. Data from [125I]rIL2 cross-linking experiments show the simultaneous expression of two IL-2 binding peptides of 70 and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the IL-2R alpha and to the IL-2R beta by the finding that these bands are abolished by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites of the alpha and beta chains. Scatchard analysis after [125I]IL-2 labelling shows the presence of both high affinity (150 sites with a Kd of 147 pM) and low affinity (1100 sites with a Kd of 4 nM) IL-2 binding sites. Northern blot and dot blot analysis show the presence of specific transcripts for the IL-2R alpha and IL-2R beta genes in early passaged fibroblasts. By contrast, in senescent cultures, only the IL-2R beta transcript were detected. Finally, IL-2 at low concentrations (36 pM) down modulates the level of the intercellular adhesion molecule ICAM-1 in young but not in senescent cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of the interleukin-2 receptor on human fibroblasts and its biological significance. 137 26

Fc receptor-positive lymphocytes (FcR+) contain lymphokine-activated killer cell (LAK) precursors that in response to IL-2 develop potent antitumor cytotoxicity. These FcR+ cells are also capable of antibody-dependent cytotoxicity (ADCC), which can be detected using fresh human peripheral blood lymphocytes (PBL) directed to murine targets, however, PBL-mediated ADCC to human tumors usually is very low, requiring a stimulation of the PBL, which also can be accomplished with IL-2. Using human melanoma tumor target cells, with and without the 14G2a monoclonal antibody, we examined in parallel the role of p75 IL-2 receptor for regulation of the induction of both LAK and ADCC forms of antitumor cytotoxicity. Enrichment of FcR+ cells from fresh peripheral blood by elutriation and flow cytometry, followed by varying periods of IL-2 culture, revealed a differential kinetics of activation. ADCC was detectable after PBL exposure to IL-2 for as short as the 4 h cytotoxicity assay, while LAK activation required more than 24 h of exposure. Elimination of the FcR+ cells by magnetic bead depletion from large granular lymphocyte populations (LGL) resulted in a loss of both LAK and ADCC. Addition of antibody known to block the binding of IL-2 to the p75 molecule of the IL-2 receptor complex (Mik-beta 1) to activation cultures at zero time resulted in abrogation of both cytotoxicities. These results suggest that differentiation and maturation of the ADCC effectors occurs in response to IL-2 via the p75 molecule, as also does LAK activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor recognition and lytic competence of IL-2-activated lymphocytes: regulation of both antibody-independent and -dependent cellular cytotoxicity via P75 IL-2 receptor. 142 May 99

Although IL-2 receptor beta chain (IL-2R beta) expressed in various lymphoid cell lines binds IL-2 with an intermediate affinity, IL-2R beta expressed in fibroblasts is unable to bind IL-2, suggesting that IL-2R beta is on its own not sufficient for generating the intermediate-affinity receptor and that lymphoid-specific regulatory control may be operated to allow IL-2R beta to bind IL-2. In the present study, we observed that human IL-2R beta expressed in a mouse myeloma X63-Ag8.653 (X63) by cDNA transfection did not bind IL-2, while the same IL-2R beta expressed in an IL-6-dependent mouse B cell hybridoma F12-28, which was obtained by cell fusion between X63 and lipopolysaccharide (LPS)-induced lymphoblasts, bound IL-2 with the intermediate affinity. Interestingly, when the human IL-2R beta cDNA-transfected X63 clone, which by itself manifests no IL-2 binding, was fused with LPS-induced lymphoblasts, the resultant hybridomas manifested intermediate-affinity IL-2 binding. The IL-2 binding was specifically inhibited by addition of antihuman IL-2R beta mAb (Mik-beta 1) but not by mAb against mouse IL-2R subunits, indicating that human IL-2R beta was responsible for the IL-2 binding, i.e. non-functional human IL-2R beta in X63 was converted to competent IL-2R beta by complementation with a mouse spleen cell-derived factor(s) through the cell fusion. Cross-linking experiments with [125I]IL-2 revealed the presence of a 61 kDa protein other than IL-2R beta in cells expressing the intermediate-affinity IL-2R.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reconstitution of the intermediate-affinity interleukin-2 receptor by cell fusion. 148 30

Recent studies have demonstrated that cyclosporin A (CyA) exerts a beneficial effect on psoriasis. It remains unclear, however, whether T-cell immune responses are definitely impaired in psoriasis and whether the anti-psoriatic effect of CyA is mediated by interference with T-cell activation. To study these questions, 20 patients with severe psoriasis were treated with oral CyA (5 mg/kg/d) for 12 weeks and examined for several phenotypic and functional properties of peripheral blood T cells before and after therapy. The analyses included CD3, CD4, and CD8 phenotypes, IL-2 production and IL-2 receptor expression following Con A stimulation, proliferative responses to PHA, and in vivo responsiveness to a foreign antigen, PPD. When the values of patients before therapy and healthy individuals were compared, no statistically significant differences were detected in any of these analyses. Furthermore, none of these T-cell properties were changed after 12 weeks of treatment. To assess possible minor mutations in T-cell-related genes in psoriasis, the T-cell receptor beta-chain locus was analyzed by Southern hybridization. With a cDNA probe for C beta 1, a polymorphic fragment of congruent to 9 kb was detected in Eco RI digests in one of 20 patients and in four of 10 healthy individuals examined. No polymorphism was detected in Bam HI digests in any individual. These results fail to support the hypothesis that a general or "systemic" alteration in T-cell immunity plays a central role in the pathogenesis of psoriasis and in the action of CyA against this skin disorder.
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PMID:Genomic, phenotypic, and functional analyses of T cells in patients with psoriasis undergoing systemic cyclosporin A treatment. 167 38

The extracellular matrix (ECM) is composed of a number of macromolecules that promote cell adhesion, cell migration, and differentiation. Receptors for these molecules have been identified and belong to a superfamily of cell surface proteins, collectively known as the integrins. In this study, we show that the matrix protein fibronectin (FN) acts synergistically with immobilized anti-CD3 antibody to promote proliferation of total human peripheral blood lymphocytes (HPBL) in the absence of exogenous IL-2. Proliferation was inhibited by both the alpha 5 beta 1 and alpha 4 beta 1 recognition peptides. ARG-GLY-ASP (RGD), and GLU-ILE-LEU-ASP-VAL-PRO-SER-THR (EILDVPST), respectively. Expression of CD25 (IL-2 receptor) was significantly higher on cells cultured on anti-CD3 and FN, indicative of T-cell activation. Additionally, cells cultured on immobilized anti-CD3 and FN for 3 days showed increased adhesion to FN and increased forward light scatter/side scatter profile. Synthesis of both IL-1 and to a lesser extent IL-2 was elevated in supernatants from cultures containing both anti-CD3 and FN. These data are consistent with published reports which demonstrate that ECM proteins can act as costimulants of lymphocyte proliferation. Finally, our results show that cells cultured on anti-CD3 antibody and FN have an activated phenotype and that cytokines may be involved in this process.
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PMID:Fibronectin augments anti-CD3-mediated IL-2 receptor (CD25) expression on human peripheral blood lymphocytes. 182 61

The human high-affinity receptor for interleukin 2 (IL-2) has been proposed as being a membrane complex composed of at least two distinct polypeptide chains: p55 (alpha chain), recognized by the anti-Tac monoclonal antibody (mAb), and p75 (beta chain), both of which are capable of binding IL-2. Whereas the alpha chain itself has been shown to be nonfunctional, the beta chain appears to be pivotal in the IL-2 signal transduction, although the beta chain is otherwise poorly characterized. Three beta chain-specific mAbs, designated Mik-beta 1, -beta 2, and -beta 3, were developed. Mik-beta 1 and -beta 2 completely inhibited the IL-2 binding to the beta chain, whereas Mik-beta 3 immunoprecipitated the beta chain crosslinked with 125I-labeled IL-2. The beta chain immunoprecipitated by these mAbs was revealed to have a Mr of 68,000-72,000. High-affinity IL-2 binding was completely abolished by Mik-beta 1. Although IL-2-dependent T-cell growth at high IL-2 concentrations was not inhibited by the anti-Tac, it was almost completely inhibited by Mik-beta 1 in the presence of the anti-Tac. These results clearly indicate that the beta chain is an indispensable component to the high-affinity IL-2 receptor and is responsible for the IL-2 signal transduction. The beta chain was found to be constitutively expressed without the alpha chain on the surface of peripheral blood Leu-19+ natural killer cells.
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PMID:Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. 246 93

Transforming growth factors beta (TGF-beta) inhibit the growth of a variety of cell types, including lymphocytes. The immunosuppressive effects of TGF-beta have been attributed to the interference of these molecules with the interleukin-2 (IL-2)-driven component of lymphocyte proliferation. In order to elucidate in more detail the effects of TGF-beta on IL-2-induced proliferation, we investigated the effects of porcine transforming growth factor beta 1 and 2 (pTGF-beta 1 and 2) on the IL-2-driven proliferation of a murine IL-2-dependent T-lymphocyte line (CTLL). The results showed that pTGF-beta 1 and 2 decreased 3H-thymidine incorporation in CTLL cells in a dose-dependent fashion (maximum decrease of 75-85%). Combined-time kinetic analysis of the effects of pTGF-beta on 3H-thymidine incorporation, cell growth, and cell-cycle distribution (monitored as DNA content distribution) revealed that, in the first 48 h of culture, pTGF-beta 1 increased the doubling time from 11.4 to 19.2 h without significantly affecting the cell-cycle distribution of CTLL cells. After 96 h of culture in the presence of pTGF-beta 1, cells started to accumulate in G0/G1, although at this time point 30% of the pTGF-beta 1-treated cells were still in S-G2/M. Furthermore, during the first 48 h, neither the expression of the 55 kd chain of the IL-2 receptor (IL-2R) nor the expression of the transferrin receptor (TfR) was affected by TGF-beta. After 72 h of culture in the presence of pTGF-beta 1, the expression of the IL-2R and TfR was decreased. The data suggest that in CTLL cells TGF-beta initially slows the progression of cells in all phases of cell cycle. In addition, the initial TGF-beta-mediated decrease of IL-2-induced 3H-thymidine incorporation and cell proliferation in CTLL cells is not due primarily to downregulation of the IL-2R and/or TfR.
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PMID:Transforming growth factors beta slow down cell-cycle progression in a murine interleukin-2 dependent T-cell line. 278 27

Triggering of integrins can deliver signals that will regulate T cell activation and proliferation when coupled with TCR/CD3 signaling. While co-activation stimuli can be achieved either with immobilized natural ligands or immobilized monoclonal antibodies specific for various integrin subunits, counterposing effects can be delivered by ligation of the integrin beta 1 chain (CD29) resulting in the downregulation of T cell proliferation. Thus, integrins may play a pivotal role in cell activation and are involved in both positive and negative regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate the role of beta 1 in the negative regulation of T cell proliferation. T lymphocytes were stimulated to proliferate when activated with immobilized mAb to CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4 (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form, mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive properties. In kinetic experiments, the addition of mAb 18D3 effectively inhibited the ultimate induction of DNA synthesis at all time points until the time coinciding with the onset of T cell proliferation, indicating that triggering the beta 1.1 epitope may only act to quench activation events prior to cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor render cells incompetent for restimulation, but appeared to selectively inhibit IL-2 synthesis with little effect on the induction of IL-2 receptor expression.
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PMID:MAb 18D3 triggering of integrin beta 1 will prevent but not terminate proliferation of human T cells. 752 62

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

To determine a role of protein kinase C (PKC) isozymes in lymphocyte activation, human peripheral blood mononuclear cells were activated with 12-deoxyphorbol-13-O-phenylacetate (dPP; an agonist of both calcium-dependent and calcium-independent PKC isozymes), thymeleatoxin (TX; an activator of calcium-dependent PKC alpha, beta, and gamma), and 12-deoxyphorbol-13-O-phenylacetate 20 acetate (dPPA; an activator of PKC beta 1 isozyme) and examined for DNA synthesis, lymphocyte proliferation, interleukin-2 (IL-2) production, expression of IL-2 receptor alpha and beta chains on CD3+, CD4+, and CD8+ T lymphocytes and CD20+ B lymphocytes, and translocation of PKC beta isozyme from cytosol to membrane fraction. The results show that dPPA activates lymphocytes by inducing the above changes in a manner analogous to that of dPP, TX, and phorbol myristate acetate. These data suggest that PKC beta 1 is involved in the activation of human peripheral blood T and B lymphocytes.
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PMID:12-Deoxyphorbol-13-O-phenylacetate 20 acetate [an agonist of protein kinase C beta 1 (PKC beta 1)] induces DNA synthesis, interleukin-2 (IL-2) production, IL-2 receptor alpha-chain (CD25) and beta-chain (CD122) expression, and translocation of PKC beta isozyme in human peripheral blood lymphocytes: evidence for a role of PKC beta 1 in human T cell activation. 792 99


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