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 short-term exposure of peripheral blood mononuclear cells (PBMC) to recombinant human interleukin-2 (rhIL-2) at 37 degrees C leads to the generation of lymphokine-activated killer (LAK) activity similar in magnitude to that obtained by the exposure of PBMC to rhIL-2 continuously for 3-5 days. In order to investigate whether the required signal for LAK induction occurred during the short exposure to rhIL-2 or at a later point in the induction phase, PBMC were exposed to rhIL-2 for 1 h at 4 degrees C and then exposed to a low-pH wash to remove bound IL-2 from its receptor. PBMC treated in such a way showed increased LAK activity and proliferation compared to cells exposed to rhIL-2 alone. Expression of the p55 (alpha) subunit of the IL-2 receptor was also increased. In order to cause the augmentation, a lowering of the pH below 4.0 was necessary, and exposure of PBMC to low pH alone (in the absence of rhIL-2) failed to cause activation. Another relevant feature was a transient increase in the expression of the p75 subunit of the IL-2 receptor (beta chain) immediately following the exposure to low pH and the release of interferon gamma, tumour necrosis factor alpha and IL-6; activation was blocked by the inclusion of neutralising antisera raised against rhIL-2 and interferon gamma, thus demonstrating that the endogenous release of these cytokines is important for activation.
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PMID:The augmentation of lymphokine-activated killer activity following pulsing of human peripheral blood mononuclear cells with recombinant human interleukin-2. 151 61

The in vitro mitogenic properties of polyclonal antithymocyte and antilymphocyte globulins (ATG) on peripheral blood mononuclear cells were investigated. The ATG were mitogenic in a dose-dependent manner with maximal proliferation observed at 250 or 500 micrograms/ml. ATG activated blastogenesis of CD4+, CD8+, and CD57+ (NK cells) lymphocytes. The ATG induced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression and lymphokine secretion in cell culture supernatant and IL-2 receptor (CD25) expression. At submitogenic concentrations ATG potentialized the effect of phorbol esters on T cell proliferation, but not that of calcium ionophore. The mitogenic effect of ATG was not abrogated by monocyte depletion indicating that like CD2 monoclonal antibodies (mAbs) ATG activate T cells via a monocyte-independent pathway. CD3 and CD2 mAbs which activate T cells without binding to B surface determinants stimulated the proliferation of B cells and their differentiation into immunoglobulin (Ig)-secreting cells. In contrast, ATG induced only a transient B cell activation, but failed to support B cell differentiation into Ig-secreting cells despite the secretion of IL-2. These properties shared by ATG obtained in horses or rabbits by immunization with different cell types appear to differ from those of other T cell mitogens.
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PMID:Monocyte-independent T-cell activation by polyclonal antithymocyte globulins. 151 79

We have evaluated the synergistic effects of interleukin-1 (IL-1) and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) activity. Subcutaneous injection of recombinant IL-1 beta at an initial dose of 1 x 10(4) U was given to nine patients (five with renal cell carcinoma, two with bladder carcinoma, one with renal pelvic tumor, one with testicular tumor) on days 1 and 2 weekly for 4 weeks. The dose was increased weekly up to 4 x 10(4) U, if it was well tolerated. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in the 2nd and 4th weeks, and LAK activity of PBMC against Daudi cells was measured using a 4-h 51Cr-release assay at an effector:target cell ratio of 20:1, after incubation with 50 U/ml of recombinant IL-2 for 72 h. Proliferation of PBMC was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 h. IL-2 receptor (IL-2R)-positive cells in PBMC were enumerated using monoclonal antibody and flow cytometry. Mean values of LAK activity induced by IL-2 were significantly augmented after administration of IL-1 beta (p less than 0.01). IL-1 beta, however, did not enhance proliferation of PBMC caused by IL-2, nor did it increase the number of IL-2R-positive cells in peripheral blood lymphocytes of the patients. Results suggest that combination of IL-1 and IL-2 has synergistic antitumor activity in treatment of malignant diseases.
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PMID:Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies. 151 24

The present study has examined the effect of GSH on two lines of IL-2-dependent activated killer cells, LAK cells and alpha CD3-activated killer (CD3-AK) cells. We found that GSH added during first 24 hr decreased the generation of LAK and CD3-AK cells from resting lymphocytes, whereas after 48 hr of activation, the addition of GSH increased the killer cell activity. In addition, BSO, an inhibitor of GSH biosynthesis, decreased the proliferation and cytotoxic activities of activated killer cells, and the inhibitory effect was reversed by GSH. These results indicate that GSH downregulates the generation of LAK or CD3-AK cells from resting lymphocytes, but it upregulates the further differentiation of preactivated killer cells. The effect of GSH thus varied with the state of activation of the killer cells. Culturing CD3-AK cells in GSH did not change the distribution of T cell subsets, did not affect the cells' ability to produce lymphokine (IL-2), and did not induce suppressor cells. One striking change as revealed by flow cytometry analysis was that the levels of IL-2 receptor and TCR (alpha/beta)-CD3 were reduced by 80 and 30%, respectively, after 48 hr culturing in GSH. Determination of the mRNA of IL-2 receptor suggests that a post-transcriptional block existed. It appears that the negative effect of GSH on the function of surface IL-2 receptors or T cell receptors on resting lymphocytes severely affected the signal transduction through these receptors and thus abrogated or reduced LAK or CD3-AK cell response. In contrast, for preactivated killer cells, upregulation by intracellular GSH of IL-2 utilization is a dominant effect, thus allowing further differentiation of these killer cells. Our results indicate that the balance between the activation signal (IL-2 or alpha CD3) and the immunoregulatory signal (induced by GSH) may determine the outcome of the immune response.
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PMID:Dichotomy of glutathione regulation of the activation of resting and preactivated lymphocytes. 153 39

Highly purified natural human interferon-alpha (IFN-alpha) inhibited in a dose-dependent manner the proliferation of human peripheral blood lymphocytes (PBL) stimulated with T-cell mitogen concanavalin A (Con A) or with interleukin-2 (IL-2). Contrary to this inhibitory effect, IFN-alpha at the same concentrations significantly increased proliferation of PBL stimulated with B-cell mitogen bacterial lipopolysaccharide (LPS) or with IL-3, and even spontaneous proliferation of PBL was enhanced by IFN-alpha. Proliferation of Con A-stimulated PBL depleted of CD8+ cells was sensitive to the inhibitory action of IFN-alpha, while proliferation of the Con A-stimulated CD4+ cell-depleted PBL was not affected by IFN-alpha. The inhibitory effect of IFN-alpha on PBL proliferation was due to neither inhibition of IL-2 receptor (IL-2R) expression, activation of suppressor cells, nor inhibition of lymphokine production. Rather, IFN-alpha augmented production of IL-1 and IL-2 by PBL. These results show that the suppressive effect of natural IFN-alpha on Con A-induced proliferation of PBL is due to a direct growth-inhibitory effect on CD4+ T cells, and that IFN-alpha simultaneously augments production of lymphokines. This could in turn lead to the increased proliferation of IFN-alpha-resistant cell populations.
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PMID:Inhibitory versus stimulatory effects of natural human interferon-alpha on proliferation of lymphocyte subpopulations. 153 94

The capacity of staphylococcal enterotoxins to stimulate all T cells bearing certain TCR variable region alleles has generated a great deal of interest. This stimulation appears to involve specific binding of the toxin to class II molecules and subsequent stimulation of the T cell via the TCR V beta elements. Recent studies from our laboratory have focused on the ability of staphylococcal enterotoxins to directly activate purified lymph node T cells and a panel of T cell clones and hybridomas. A T cell costimulation assay was performed to assess cellular activation requirements and cytokine receptor expression. Activation of highly purified lymph node T cells by staphylococcal enterotoxin B (SEB) required costimulatory signals which could be provided by IL-1, IL-2, IL-4, or IL-6, whereas SEB alone demonstrated no significant proliferative response. Using a panel of TH1 and TH2 cell clones and T cell hybridomas possessing various responsive and nonresponsive V beta alleles, it was possible to demonstrate that SEA and SEB costimulate T cells via the TCR complex. Additionally, enterotoxin-pretreated T cells demonstrated a significant proliferative response upon exposure to class II-bearing accessory cells, suggesting that these toxins bind directly to T cells. Highly purified T cells cultured with both SEB and IL-1 exhibit significantly increased levels of IL-2 receptor, whereas cells cultured with SEB or IL-1 alone demonstrated low levels of this receptor. These results do not exclude an association of the staphylococcal enterotoxins with class II molecules in a manner which results in a high avidity binding to the TCR required for transduction of the appropriate activation signals. In the absence of class II molecules, however, these superantigens can still bind to T cells, and the activation signal is delivered in the presence of cytokines that trigger T cell growth and lymphokine production.
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PMID:Direct activation of murine T cells by staphylococcal enterotoxins. 154 63

Recently, interleukin 2 (IL-2) has been shown to induce increased activity of the p56lck protein-tyrosine kinase (PTK) in T-cell and natural killer cell lines, and evidence for a direct interaction between the p75 subunit of the IL-2 receptor (IL-2R) and this src-family kinase has been reported. Though these findings suggest a central role for lck in IL-2 signal transduction, one problem with this idea is that not all IL-2-responsive cells express the lck gene. For this reason, we examined the effects of IL-2 on the activity of src-like kinases in a pro-B cell line, F7, that lacks p56lck but that displays high-affinity IL-2Rs and vigorously proliferates in response to this lymphokine. Of the eight known src-family PTKs, F7 cells were shown to contain only p53/56lyn, p59fyn, and a small amount of p62yes. Stimulation of resting F7 cells with IL-2 induced a rapid (detectable within 1 min and maximal at 15 min) and concentration-dependent increase in the specific activity of p53/56lyn kinase, as assessed by in vitro kinase assays. This effect of IL-2 on p53/56lyn kinase was specific, since no IL-2-inducible changes were detected in the activities of the p59fyn and p62yes kinases. Furthermore, by using a monoclonal antibody specific for the approximately 75-kDa beta subunit of the IL-2R (referred to as p75/IL-2R beta), evidence for physical association between the lyn kinase and the IL-2R complex was obtained, in that a small proportion of the p53/56lyn kinase in F7 cells, but no detectable p59fyn kinase, was coimmunoprecipitated with p75/IL-2R beta. When combined with the recent evidence that IL-2 regulates p56lck in T cells, these results indicate that some flexibility exists in the ability of various src-like PTKs to participate in IL-2 signal transduction mechanisms and raise the possibility that lineage-specific (T-versus B-cell) responses to IL-2 may be determined at least in part by the repertoire of src-like PTKs expressed in the cell.
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PMID:Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line. 155 73

A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.
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PMID:Interleukin-2-induced increase of a monoclonal B-cell lymphocytosis. A novel in vivo interleukin-2 effect? 156 83

Minimal change nephrotic syndrome has been reported to be a lymphocyte-mediated disorder. It has been suggested that the secretion of lymphokine(s) is involved in the pathogenesis of MCN and in determining proteinuria. The presence of a soluble form of IL-2 receptor (sIL-2R) has been previously described in the sera of patients with some autoimmune disorders. In this work, we report the detection of high sIL-2R levels, both in the plasma (mean value 844 +/- 436 U/ml versus normal value 276 +/- 86 U/ml) and urine of patients with MCN during the nephrotic phase alone. Instead, when the patients achieve stable remission, sIL-2R levels decrease to within normal values (mean value 332 +/- 272 U/ml). Furthermore, during the nephrotic syndrome we observed a significant inverse relationship between sIL-2R plasma levels and the mitogenic response to PHA (p less than 0.005). Since sIL-2R exerts a down-modulation on T-proliferative expansion, sIL-2R might represent one of the inhibitory serum factors extensively reported in the serum of patients with MCN-induced nephrotic syndrome.
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PMID:Lymphocyte release of soluble IL-2 receptors in patients with minimal change nephropathy. 158 55

In vivo and in vitro productions of interleukin-2 (IL-2), IL-2 receptor (IL-2R) and gamma-interferon (gamma-IFN) in 64 multi-transfused thalassemic patients and 20 healthy children were studied. The results were: 1) Increased serum concentrations of IL-2 and IL-2R, and decreased serum concentration of gamma-IFN were found in thalassemic patients when compared to controls. 2) In in vitro study, productions of IL-2, IL-2R and gamma-IFN were much lower in thalassemic patients than in controls. The possible mechanisms for the altered lymphokine productions are discussed.
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PMID:In vivo and in vitro productions of interleukin-2, interleukin-2 receptor and gamma-interferon in multitransfused thalassemic patients. 162 46


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