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 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

Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2.
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PMID:In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses. 819 81

Age-associated thymic involution manifests its effects in a variety of ways that are related to a loss of T cell function. These include the appearance of a non-functional subset of T cells that increase in representation with age. Moreover there is a loss of T cell proliferative ability, a decline in the synthesis and release of interleukin-2 (IL-2), a decline in the ability of the T cell to express the IL-2 receptor, and a loss of control activity. This loss of control is demonstrated by the age-related appearance of autoantibodies and an increase in the elaboration of inflammatory cytokines such as TNF, IFN, IL-6, and TGF. A major part of the basis for the loss of T cell function is an inability of the T cell to respond to activation signals that are transmitted through the membrane binding of specific stimulatory signals. Transduction events, differentiation signals, and a loss of control mechanisms are all parts of a complicated picture of age-related immune deficiencies.
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PMID:Age-related effects in T cell activation and proliferation. 822 30

Excessive B cell function including autoantibody production is a common feature of SLE and considered to be intimately associated with spontaneous lymphokine secretion by themselves. To clarify roles of IL-6/IL-6 receptor autocrine activation pathway in autoantibody production observed in patients with SLE, we studied expression and function of IL-6 receptors in comparison with those of IL-2 receptors, Tac on SLE B cells. IL-6 receptors and IL-2 receptors have been detected on B cells in the blood without any in vitro stimuli in most patients with SLE. The introduction of anti-IL-6 receptor antibody, which inhibits binding to the receptors of IL-6, and anti-IL-2 receptor antibody, anti-Tac to the cultures of SLE B cells resulted in potent inhibition of spontaneous production of polyclonal Ig and anti-DNA autoantibodies. In addition, fresh SLE B cells secreted high levels of IL-6 without any in vitro stimuli. These results indicate that constitutive expression of IL-6 receptors on B cells in conjunction with spontaneous IL-6 production by B cells induces autocrine B cell activation, which may lead to B cell hyperactivity and autoantibody secretion in SLE patients. Dysregulation of B cell activity observed in patients with SLE could thus be, at least in part, independent of T cell help.
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PMID:Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. 824 83

The pathophysiology of psychotic and other symptoms in schizophrenia remains a mystery despite decades of research. Even though it has been suspected for many years that autoimmune mechanisms may play a role in the pathophysiology of schizophrenia, firm evidence for this hypothesis has been lacking. Our studies, over the last 10 years, have revealed that a subgroup of schizophrenics have several significant immunological abnormalities, including increased prevalence of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased serum IL-2 receptor concentration, increased serum IL-6 concentration, and an association with HLA antigens. These findings are characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and insulin-dependent diabetes mellitus. We also found that some schizophrenics have antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL-2 production. None of the above findings can be interpreted as definitely confirming the role of autoimmunity in schizophrenia. Nevertheless, taken together, the recent evidence points towards the existence of a subgroup of schizophrenics who have immunological findings consistent with that hypothesis. Further studies directed at finding the brain antigens targeted by the immune system in these patients, and longitudinal studies correlating clinical and immune changes over time, are needed.
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PMID:Autoimmunity in schizophrenia: a review of recent findings. 825 Nov 50

Recent observations have demonstrated the presence of activated T lymphocytes and macrophages in human atherosclerotic lesions. Cells found within these lesions produce cytokines that alter vascular homeostasis in a manner that promotes atherogenesis. To elucidate the role of these immunocompetent cells in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic features of the cellular infiltrates was studied in normal aortas from children; and in later phases of the disease (including fatty streaks and fibrous or atheromatous plaques). Semi-quantitative analysis of cytokine-expressing cells was also investigated with serial sectioning. In 4 of 9 young subjects, the grossly normal aorta contained relatively cell-rich areas which were located preferentially around the ostia of intercostal arteries and were composed of isolated or layered T lymphocytes and macrophages. In these prelesional areas, interleukin-1 (IL-1), IL-2 receptor (IL-2R) and tumour necrosis factor (TNF) were detected in the cytoplasm of the infiltrating cells, whereas no detectable reactivity was noted for IL-2, IL-6, interferon-gamma (IFN-gamma) or lymphotoxin (LT). In fatty streaks and full-grown atheromas including "cap" and "shoulder" regions, various numbers of T lymphocytes, macrophages and macrophage foam cells were present. In these lesion areas, especially where the cellular infiltrates were numerous, macrophage foam cells and smooth muscle cells expressed not only IL-1 and TNF but also IL-6. The ratio of IL-2R positive cells showed a tendency to decrease with advance of the disease process. Electron-microscopic examination of lesion areas demonstrated ultrastructural aspects of the cognate cell-to-cell interaction, as shown by the direct apposition of lymphocytes to macrophages or macrophage foam cells. These results suggest that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherosclerosis.
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PMID:Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis. 829 Dec 16

We used a mixed leucocyte culture between human T cells and irradiated murine splenocytes which allowed us to distinguish between cytokine production from the responder and stimulator cells by the use of species-specific assays for mRNA up-regulation. Using this model of T cell activation by antigen, we studied the effects of human antigen-presenting cell-derived cytokines IL-1 beta, IL-6 and TNF-alpha on the activation of human T cell subsets. We show in this system that exogenously added IL-1 beta, IL-6 and TNF-alpha induces IL-2 receptor (R) up-regulation and IL-2 production, and proliferation by both CD4+ and CD8+ cells. The addition of IL-1 beta induces IL-6 mRNA, and anti-IL-1 antibodies or an IL-1R antagonist protein completely suppresses IL-6 and TNF-alpha supported proliferation. Similarly, addition of IL-6 or TNF-alpha induces up-regulation of IL-1 beta mRNA. However, anti-IL-6 and anti-IL-6R antibodies only partially block proliferation supported by IL-1 beta. These findings suggest that IL-6 and TNF-alpha will induce IL-2R up-regulation/IL-2 secretion via the induction of IL-1 beta production.
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PMID:Interaction of IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in human T cells activated by murine antigens. 837 Jan 77

To study the role of interleukin (IL)-6 as a growth and differentiation factor for Epstein-Barr virus (EBV)-transformed B lymphocytes, we transfected the cDNA coding for human IL-6 in a monoclonal IgG1-secreting EBV B cell line. Two independent clones were selected that constitutively secreted high amounts of IL-6. These clones showed enhanced levels of IL-6 and tumor necrosis factor alpha secretion when compared to non-IL-6 transfected controls. Moreover, they could efficiently be recovered from low cell density cultures in limiting dilutions when plated on a feeder layer of heterologous EBV B cells. IL-6-induced phenotypical changes comprised a significant rise in immunoglobulin secretion levels and enhanced membrane expression of CD25 (the beta chain of the IL-2 receptor) and of the B cell differentiation antigen CD40. IL-6-dependent down modulation of CD38 and of the adhesion structure VLA4 were also observed. Our data support the notion that IL-6 can serve as an growth and differentiation factor for EBV B cells.
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PMID:Expression of the IL-6 gene induces differentiation of a human monoclonal EBV-transformed B cell line. 839 33

Immune and inflammatory responses involve a whole array of cells and cell products which interact and mutually regulate each other. Many of these interactions are mediated by cytokines acting through specific receptors. Furthermore, lipid mediators such as PAF and the arachidonic acid metabolites LTB4 and PGE2 are known to affect several of the mechanisms involved in the regulation of the immune and inflammatory responses. In this paper, we review recent data from our laboratory illustrating the differential regulation of IL-6 and TNF alpha production and IL-2 receptor alpha and beta expression by these lipid mediators. We show that the regulation of these genes is both transcriptional and post-transcriptional, and that LT and PG can also be involved as second messengers in these regulatory processes.
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PMID:Differential regulation of cytokine and cytokine receptor genes by PAF, LTB4 and PGE2. 839 42

We analyzed T cell responses through the CD3 activation pathway in a group of chronic HBV carriers. PBMC stimulated with the mAb OKT3 showed higher proliferative response in HBV-DNA(-) carriers compared to HBV-DNA(+) carriers and to controls. In contrast, no differences in proliferative responses were observed between HBV-DNA(-) carriers and controls in cell cultures stimulated with immobilized 64.1 mAb (SPB-64.1) which induces proliferation in the absence of monocytes. We further examined T cell responses in the presence of monocytes and their soluble factors to immobilized OKT3 mAb (SPB-OKT3). Purified T cells did not proliferate to SPB-OKT3. When autologous monocytes were added, higher proliferative response, IL-2 production, and IL-2 receptor expression were observed in HBV-DNA(-) carriers than in controls. An enhanced cell proliferation was also obtained when monocyte supernatants were added to T cells cultured with SPB-OKT3. Moreover, when IL-6 alone or combined with IL-1 was added to SPB-OKT3-stimulated T cell cultures, a significantly higher increase in T cell proliferation was detected in HBV-DNA(-) carriers. Our results thus show a T cell hyperreactivity to accessory signals from monocytes (mainly IL-6) in HBV-DNA(-) carriers, that is probably related to an ongoing viral clearance.
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PMID:Anti-CD3-activated T cells from chronic nonviremic HBV carriers are hyperreactive to monocytic accessory signals. 840 55


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