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)

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

It has recently been demonstrated that IL-4 inhibits IL-2 receptor expression on T cells. Studies have also shown that IL-4 can inhibit IL-2-induced natural killer cell (NK) cytotoxicity, and that IL-4 in combination with IL-2 and large granular lymphocyte (NK/LGL) cells suppresses Ig synthesis. Therefore, we examine whether IL-2 receptor expression on NK/LGL cells is affected with or without IL-4, using fluorescent receptor analysis. Our results demonstrate that IL-4 inhibits/down-regulates the expression of IL-2 receptors on either phytohemagglutinin or IL-2-stimulated NK/LGL cells.
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PMID:Down-regulation of interleukin-2 receptor expression on natural killer cells/large granular lymphocytes by interleukin-4. 157 Oct 94

Radix Tripterygium wilfordii Hook-F (TW) is a Chinese herbal medicine that has been reported to be effective in the treatment of various autoimmune disorders in experimental animals and man. Little is known about the immunosuppressive mechanism of action of this medicine. We demonstrate herein that TW is capable of inhibiting several afferent immune functions including the in vitro response of human peripheral blood mononuclear cells to both mitogen and alloantigen, and the generation of cytotoxic T cells. This inhibition is likely mediated through a reduction in both IL-2 production and IL-2 responsiveness. TW evidenced little capability of impairing IL-2 receptor expression, or efferent immune mechanisms such as cell-mediated cytotoxicity or natural killer cell-mediated cytotoxicity. The immunosuppressive effects of TW were reversible except at the highest concentration tested, 2.4 micrograms/ml, and there was no evidence of TW-mediated cell-well damage as evidenced by trypan-blue exclusion. TW, or some of its constituents, may be important new agents to be studied for immunosuppression in organ transplantation.
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PMID:Radix Tripterygium wilfordii--a Chinese herbal medicine with potent immunosuppressive properties. 236 55

A series of experiments examined effects of stressful conditions on several cellular immune responses and attempted to elucidate the physiological mechanisms underlying these effects. Initial studies showed that stressful conditions can profoundly suppress immune responses of blood and splenic lymphocytes, including T-cell mitogenesis, natural killer cell activity, production of interleukin-2 (IL-2) and interferon and IL-2 receptor expression. Subsequent studies found that (1) multiple physiological pathways mediate stress-induced suppression of these responses; (2) stress-induced suppression of these responses is produced, at least in part, by a peptide with molecular weight greater than 10 kilodaltons, which stressed animals release into circulation; (3) whereas most stressful conditions suppress immune responses, stressful conditions of moderate intensity can enhance cellular immune responses; and (4) extremely small quantities of interleukin-1 (IL-1) acting in the brain (e.g., 3.1-12.4 X 10(-15) moles) bring about suppression of cellular immune responses very rapidly and for a prolonged period of time. The relationship between the newly-discovered immunosuppressive influence of IL-1 in the brain and immunosuppression produced by stressful conditions remains to be determined.
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PMID:Behavioral and neural influences on cellular immune responses: effects of stress and interleukin-1. 265 30

We studied natural killer cell-mediated (NKCM) activity and its enhancement by interleukin-2 (IL-2) in 15 patients with mixed connective tissue disease (MCTD). The mean baseline NKCM activity of peripheral blood mononuclear cells (MNC) against K562 target cells in the 51Cr release assay was found to be similar to that found in age/sex-matched controls. MCTD patients' cells, however, responded significatively less to IL-2 induction of NKCM than did those of the controls. Using the single-cell agarose NK assay, we found that MCTD patients have a small number of active NK cells that exhibit a high rate of recycling capacity in the baseline state. These preactivated cells could not be stimulated further by IL-2. In two MCTD patients the response to IL-2 was nil, and in the serum from both of them we found an IgM inhibitory factor of such IL-2 induced enhancement. This factor could be absorbed only partially by normal MNC and NK cell-depleted MNC but completely by an IL-2-dependent T-cell line, suggesting that the inhibitory factor may be acting on the IL-2 receptor. These findings seem to be different from those reported in systemic lupus erythematosus and strengthen the notion that MCTD is due to a different immunoregulatory aberration.
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PMID:Natural killer cell-mediated activity in mixed connective tissue disease and its response to induction by interleukin-2. 661 47

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, has been shown to suppress a variety of interleukin-2-(IL-2)-dependent cellular functions in both murine and human lymphocytes. These effects were examined in both human peripheral blood lymphocytes (hPBL) and the IL-2-dependent murine cytotoxic T-cell line CTLL-2. Interleukin-2-induced thymidine uptake and uridine uptake were suppressed in a dose related manner when cells were co-incubated for 48 h with 100 U rhIL-2/ml and 1-10 micrograms THC/ml. Interleukin-2-induced protein synthesis was also suppressed in a dose related manner over this THC concentration range, with the hPBL being more susceptible to the suppressive effect of THC than the CTLL-2 cells. Autoradiographic analysis of the synthesized proteins from hPBL cell lysates reveals a generalized suppression of all nascent proteins in THC-treated cultures. Human natural killer cell activity is only affected at the highest concentration tested (10 micrograms THC/ml) while lymphokine-(IL-2)-activated natural killer cell activity is affected throughout the range of 1-10 micrograms THC/ml. Together these results suggest that THC interferes with the IL-2:IL-2 receptor signaling cascade at one or possibly many points causing a decrease in IL-2-induced metabolic activity and cytolytic function.
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PMID:Delta-9-tetrahydrocannabinol treatment results in a suppression of interleukin-2-induced cellular activities in human and murine lymphocytes. 752 19

Interleukin 12 is a heterodimeric cytokine involved in the regulation of natural killer cell and T lymphocyte responses. In previous studies, we found that IL-12 induces proliferation of T cells only after co-stimulation with lectin, alloantigen, or anti-CD3 antibody. The IL-2-mediated proliferation of long-term T cell lines generated in this fashion is typically insensitive to the immunosuppressive agent, cyclosporine but sensitive to rapamycin. In this study, we examined the effect of cyclosporine and rapamycin on T cells responsive to IL-12. For long-term cultured T cell lines stimulated with phytohemagglutinin, alloantigen, or solid-phase anti-CD3 antibody, rapamycin blocked IL-12-induced proliferation to background levels. Culture in cyclosporine produced minimal inhibition of IL-12-induced T cell proliferation. Freshly isolated CD3+ cells did not proliferate in response to IL-12, nor did culture of these cells in IL-12 lead to upregulation of IL-2 receptor. These data suggest that the effect of IL-12, an important growth regulator for activated T lymphocytes, may involve late cellular activation events.
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PMID:Evidence that rapamycin inhibits interleukin-12-induced proliferation of activated T lymphocytes. 797 15

A human B-cell line (Hairy-BM) constitutively secreting interleukin-2 (IL-2) was established from tumor tissue resected surgically from a patient with breast cancer. Hairy-BM was found to be 100% CD20+, 98% surface immunoglobulin (sIg) G+, 98% sIg kappa chain+, 100% HLA-DR+, 94% IL-2 receptor (IL-2R alpha), 98% IL-2R beta, and devoid of T-cell, monocyte, and natural killer cell surface antigens. The B-cell origin of Hairy-BM was also confirmed by clonally rearranged Ig heavy- and Ig light-chain genes. The growth of Hairy-BM expressing IL-2R was promoted by recombinant IL-2 (rIL-2) and anti-CD25 antibody significantly blocked the growth enhancement. IL-2 secretion from Hairy-BM was confirmed by radioimmunoassay. By using a sensitive polymerase chain reaction technique, we demonstrated that Hairy-BM expressed IL-2 mRNA, IL-2R alpha mRNA, and IL-2R beta mRNA. These findings indicate that certain B-cells not only produce, but also respond to IL-2 in an autocrine fashion with increased proliferation.
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PMID:Interleukin-2 (IL-2) production by human B-cell line. 799 58

SCID X1 is characterized by faulty T-cell and natural killer cell differentiation caused by mutation of the gamma-c chain gene encoding a number of multiple cytokine receptors (interleukin-2 [IL-2], IL-4, IL-7, IL-9, and IL-15 receptors). To assess the feasibility of inducing long-term expression and function of the gamma-c chain, Epstein-Barr virus (EBV)-transformed B-cell lines from two patients with SCID X1 were transduced with a Moloney-derived retroviral vector containing the gamma-c chain cDNA. The viral LTR was used as the promoter. Immediately after two cycles of coculture with the psi-crip clone producing the MFG(B2)-gamma-c cDNA vector, gamma-c expression, assessed by detection of the mRNA and membrane protein expression, was found in 15% to 20% of cells. The degree of membrane expression was similar to that in control EBV-B cells. Expression increased steadily over 6 months, becoming detectable in 100% of cells, and remained stable thereafter for a total of 9 months, reflecting positive selection of transduced cells. A study of provirus integration sites showed multiple integration. The expressed gamma-c was functional, because it restored high-affinity IL-2 receptor binding, IL-2 endocytosis, and IL-2-triggered phosphorylation of JAK-3 tyrosine kinase. Similar results were obtained with the two B-cell lines. These results show that efficient gamma-c gene transfer into B-cells lacking functional gamma-c is feasible and results in strong and stable expression of a functional gamma-c chain, apparently conferring a selective growth advantage in culture. Further in vitro studies of gamma-c gene transfer into gamma-c- hematopoietic progenitors are being conducted to assess the feasibility of correcting lymphocyte differentiation defects.
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PMID:gamma-c gene transfer into SCID X1 patients' B-cell lines restores normal high-affinity interleukin-2 receptor expression and function. 860 24

Mutation of the gamma c chain common to interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15 receptors has been shown to be responsible for the X chromosome-linked severe combined immune deficiency (SCIDX1). Human SCIDX1 patients are characterized by an absence of T and natural killer cell differentiation. We report the case of a SCIDX1 patient who first had few detectable peripheral T cells, then developed, after haploidentical T-depleted bone marrow transplantation (BMT), up to 2,000/microL autologous T cells. These T cells have persisted over 8 years after BMT and were able to proliferate in the presence of mitogens and of some antigens, although to a lesser extent than control T cells. A stop mutation was identified which predicts that the major part of the cytoplasmic tail of gamma c is truncated. This mutation does not affect high-affinity IL-2 binding, but it partly decreases IL-2 endocytosis and prevents the downmodulation of the IL-2-receptor beta chain and the tyrosine phosphorylation of Jak 3 protein in response to IL-2. This report raises questions concerning the role of the gamma c chain in IL-2 receptor endocytosis and in T-cell development and differentiation.
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PMID:T-lymphocyte differentiation and proliferation in the absence of the cytoplasmic tail of the common cytokine receptor gamma c chain in a severe combined immune deficiency X1 patient. 878 27


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