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)

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.
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PMID:Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis. 807 27

We have recently shown that a single transfusion of red blood cells to normal human volunteers significantly increases the secretion of a variety of cytokines. In the present study we explored the in vitro effect of whole red blood cells on various T cell and monocytes functions of autologous human or mouse origin. This in vitro model would allow us to further determine in future studies the membranal determinants or the intracellular products of the RBC responsible for the enhancing effect. We demonstrate in this study that addition of autologous erythrocytes to human mononuclear cells or mouse spleen cell cultures results in enhancement of cellular responses to suboptimal concentrations of mitogens. These include cell proliferation, the secretion of IL-2, colony stimulating factor (CSF), interferon-gamma, tumor necrosis factor, and interleukin-6 by human MNC, and cell proliferation, IL-2, IL-3, and CSF by mouse spleen cells. The enhancing effect was dose dependent. Moreover, RBC are shown to directly enhance the expression of IL-2 receptors on both human and mouse cells without the need for the presence of mitogenic stimulation. The expression of IL-2R was measured both by acquisition of responsiveness to exogenous recombinant IL-2 and by immunofluorescence staining. We suggest that whole red blood cells exert a general enhancing effect on the secretion of a variety of cytokines and induce IL-2 receptor expression, probably through nonspecific interaction between membranal domains on erythrocytes and CD2 antigen on T cells.
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PMID:Enhancing effects of autologous erythrocytes on human or mouse cytokine secretion and IL-2R expression. 809 64

Many of the biological activities of cytokines are similar to clinical manifestations and abnormalities of laboratory parameters observed in chronic liver diseases (CLD). Evidence of impaired cytokine synthesis in CLD comes from studies of serum or plasma levels, supernatants of peripheral blood mononuclear cells stimulated with various agents and from studying cytokine expression locally in the liver. Circulating levels of several cytokine-regulated molecules such as neopterin, soluble IL-2 receptor, adhesion molecules, and metabolites of the nitric oxide pathway are elevated in patients with CLD. Thus inhibition of cytokine synthesis or modulation of their activity could provide not only important information about their pathophysiologic relevance but also have a profound impact on disease progression in CLD. These studies will also show whether prolonged anti-cytokine treatment with interleukin-1- or tumor necrosis factor-inhibitors interferes with host defense mechanism.
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PMID:The role of cytokines in the pathophysiology of chronic liver diseases. 812 73

Using enzyme-linked immunoabsorbent assays for the soluble tumor necrosis factor (TNF) receptors type I (p55) and type II (p75) and IL-2 receptor we determined their levels in the plasma of 378 patients with various solid carcinomas, 56 patients with benign tumors, and 241 healthy controls. The plasma concentrations of both TNF receptors as well as the IL-2 receptor were significantly higher in the cancer patients than in the healthy controls, independent of the origin or histology of the tumor. The incidence and the extent of the receptor increase correlated with the extent of the disease. In the patients with benign tumors plasma levels of TNF receptor p75 and IL-2 receptor were not significantly different from the controls.
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PMID:Increased plasma concentrations for type I and II tumor necrosis factor receptors and IL-2 receptors in cancer patients. 814 26

Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS.
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PMID:Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. 814 43

The present study investigates the effect of transforming growth factor (TGF)-beta on the production of IL-4 and IFN-gamma by the leukemia Th0 type cell line HUT78, by freshly isolated human T cells, and by antigen specific human T cell clones. We found that IL-4 and IFN-gamma, but not IL-2, production by stimulated HUT78 cells was inhibited by TGF-beta 1. TGF-beta 1 also reduced the accumulation of IL-4 and IFN-gamma specific mRNA in stimulated HUT78 cells. However, IL-2 and IL-7 co-stimulated IL-4 and IFN-gamma production, whereas IL-1, IL-3, IL-5, IL-6, IL-8, tumor necrosis factor-alpha or granulocyte macrophage colony stimulating factor had no effect. Because IL-2 is an important helper cytokine for the production of IL-4 and IFN-gamma, we investigated whether signal transduction through the IL-2 receptor is impaired by TGF-beta 1. We found that tyrosine phosphorylation in response to IL-2 in HUT78 cells was strongly inhibited by a short preincubation with TGF-beta 1. Evidence for an antagonistic role for TGF-beta 1 and IL-2 comes from the finding that high doses of IL-2 could partially overcome TGF-beta 1 mediated inhibition of IL-4 and IFN-gamma production. Similar to its effect on HUT78 cells, TGF-beta 1 also inhibited IL-4 and IFN-gamma production by freshly isolated T cells as well as by human T cell clones. Taken together, our experiments show that the IL-2 dependent cytokines IL-4 and IFN-gamma are both negatively controlled by TGF-beta under conditions where IL-2 production is unaffected by a mechanism which partially involves an inhibition of IL-2/IL-2R signal transduction. These data identify TGF-beta and IL-2 as mutual antagonists in the regulation of IL-4 and IFN-gamma production.
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PMID:Transforming growth factor-beta inhibits IL-4 and IFN-gamma production by stimulated human T cells. 818 98

In this review, we summarize the cellular and molecular events in the rejection of transplanted allografts, as well as the rationale for the evolving techniques to suppress such rejection. Allogenic major histocompatibility complex antigens expressed on the allograft and/or on the "passenger leukocytes" within the graft are the major antigenic stimuli recognized as being foreign by receptors of CD4+/T helper cells of the host. Host macrophages provide a second signal, interleukin (IL) 1, essential to the activation of T helper cells. Subsequent production of IL-2 by T helper cells leads to activation and proliferation of cytotoxic T cells and lymphokine-activated killer cells and the release of IL-4 and IL-6. In addition, IL-2 promotes release of interferon gamma as well as tumor necrosis factor and other proinflammatory cytokines. Therapeutic options to "downregulate" this cascade have gradually evolved from global nonspecific immunosuppressive techniques (total body irradiation, antilymphocyte serum) to increasingly specific modalities currently being studied, including monoclonal antibodies against the IL-2 receptor (thus targeting only vigorously proliferating T cells), antibodies against specific cytokines (interferon gamma, tumor necrosis factor), and now "designer" antibody-toxin conjugate molecules that deliver toxins to selected receptor targets. Finally, work continues toward inducing preoperative antigen-specific (graft) tolerance, including utilization of gene transfection techniques to transfect donor major histocompatibility complex antigens to recipients before surgery, which has been shown to prolong murine cardiac allografts, perhaps by priming specific suppressor cells. Further understanding of the initiation of, and subsequent events in, transplantation rejection will lead to increasingly effective prolongation of graft survival while minimizing adverse effects on the host.
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PMID:Transplant rejection. Mechanisms and treatment. 844 82

Cancer patients undergoing interleukin (IL)-2-based immunotherapy frequently experience dose-limiting side effects believed to be caused by the actions of such cytokines as IL-1 beta, tumor necrosis factor (TNF)-alpha and -beta, and interferon-gamma (IFN-gamma). Human peripheral blood mononuclear cells (PBMC) or monocyte-depleted peripheral blood lymphocytes were stimulated for up to 7 days by either of 2 IL-2 analogues (R38A or F42K) that bind to the intermediate-affinity IL-2 beta gamma receptor but have reduced abilities to bind the high-affinity IL-2 receptor. We previously reported that these IL-2 analogues retain the ability to generate lymphokine-activated killing by PBMC. In this study, we analyzed the cytokine content of supernatants from stimulated PBMC and peripheral blood lymphocyte cultures by enzyme-linked immunosorbent assay. The secretions of IL-1 beta, TNF-alpha, and -beta, and IFN-gamma induced by either R38A or F42K were markedly reduced compared with secretions produced in response to recombinant wild-type IL-2. In 4 experiments, secretion was reduced an average of 39% for IL-1 beta, 57% for TNF-alpha, 83% for TNF-beta, and 86% for IFN-gamma. Polymerase chain reaction analysis of recombinant wild-type IL-2 or analogue-stimulated PBMC did not reveal the presence of IL-2 mRNA; thus, differential production of endogenous IL-2 could not account for these findings. These data suggest the interaction of IL-2 and the high-affinity IL-2 receptor on human PBMC or peripheral blood lymphocyte is required for maximal secretion of IL-1 beta, TNF-alpha, TNF-beta, and IFN-gamma. Because such cytokines are believed to mediate the toxicity seen with IL-2-based immunotherapies, IL-2 analogues with reduced binding to the high affinity IL-2 receptor may prove to be an effective and less toxic means of cancer treatment.
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PMID:Human interleukin 2 analogues that preferentially bind the intermediate-affinity interleukin 2 receptor lead to reduced secondary cytokine secretion: implications for the use of these interleukin 2 analogues in cancer immunotherapy. 849 22

The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Although tumor necrosis factor-alpha (TNF) is constitutively expressed in human and mouse thymus, the effects of TNF on thymocyte proliferation, differentiation and survival suggest that its influence in the thymus is complex. To determine if this complexity results from changes in the expression of the two TNF receptors during thymocyte differentiation, we examined the expression of the 55 kDa TNF receptor (TNF-R1) and the 75 kDa TNF receptor (TNF-R2) on postnatal human thymocytes. Both TNF-R1 and TNF-R2 mRNA were found in resting human thymocytes by reverse transcriptase-polymerase chain reaction (RT-PCR). Using mAb which specifically react with the respective TNF receptors and a highly sensitive, three-step method of immunofluorescence, cell surface TNF-R1 was detected on the vast majority of thymocytes. In contrast, detectable cell surface TNF-R2 was present on a mean of only 12.9% of thymocytes. TNF conjugated to phycoerythrin (TNF-PE) also reacted with a small population of thymocytes and was found to specifically block binding of the TNF-R2 mAb and not the TNF-R1 mAb, implicating preferential binding of TNF-PE to TNF-R2. Using dual-color immunofluorescence with TNF-PE we found that the population of cells which express TNF-R2 also express high levels of the TCR alpha, beta-CD3 complex, CD4 or CD8, and IL-2 receptor alpha chain. Thus, immature (TCRneg/low) thymocytes express TNF-R1 while mature (TCRhigh) thymocytes can also express TNF-R2. This differential expression of TNF receptors provides a mechanism for distinct effects of TNF on immature vs. mature thymocytes.
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PMID:Characterization of TNF receptors on human thymocytes. 852 4


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