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)

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
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PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

A simple, one-step quantitative assay for the detection of biologically active interleukin-2 (IL-2) is described. It is based on culture of pure CD3+ T cells which have been positively selected from blood mononuclear cells by particle (M450)-bound anti-CD3 monoclonal antibody (mAb). During culture, activation of the T cells via CD3 will occur, leading to expression of IL-2 receptors but not IL-2 production. By adding IL-2 a proliferative response is evoked, giving a linear dose-response curve for IL-2 concentrations between 0.01-20 U/ml. The cells were unresponsive to IL-1, IL-4, tumor necrosis factor alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, phytohemagglutinin and concanavalin A. The responsiveness to IL-2 was enhanced by TNF-alpha and inhibited by IFN-alpha, while the other tested lymphokines and mitogens did not influence the proliferative response. Antibodies to IL-2 and to IL-2 receptor suppressed the IL-2 response in a dose-dependent manner. The method is both simple and specific, and obviates the necessity for keeping assay cells in long term culture.
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PMID:A simple and sensitive bioassay for the detection of IL-2 activity. 297 83

There is now good evidence that anti-thyroid drugs such as methimazole have immunomodulatory effects which may be important in the treatment of patients with Graves' disease, but the immunological mechanisms by which these agents act are not clear. This study has examined the effect of methimazole on four important soluble mediators of the immune response, interleukin-1 (IL-1), interleukin-2 (IL-2), gamma-interferon (gamma-IFN) and B-cell differentiation factor (BCDF). When peripheral blood mononuclear cells from normal subjects were stimulated with mitogens (phytohaemagglutinin, concanavalin A or pokeweed mitogen) in the presence of 10-100 mumol/l methimazole, there was an increase in IL-2 activity in the culture supernatants. This effect was apparent between 24 and 60 h: enhanced proliferation of T-cells was also seen in methimazole-supplemented cultures. There was no effect of the drug on IL-2 receptor expression or on IL-1 and gamma-IFN production. BCDF was increased by methimazole in one of three experiments with pokeweed mitogen but not in three experiments with concanavalin A. These results suggest that the enhancement of mitogen-stimulated T-cell proliferation in vitro with methimazole is due to an increase in the IL-2 available to the T-cells in these cultures. Thus the in-vivo immunological effects of these drugs are likely to be complex since they may have at least two, possibly related, actions on the intrathyroidal lymphoid infiltrate, namely inhibiting oxygen radical generation and increasing IL-2 levels.
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PMID:Effect of the anti-thyroid drug methimazole on interleukin-1 and interleukin-2 levels in vitro. 309 61

We have previously reported that mouse bone marrow (BM) cells stimulated with alloantigen produce cytotoxic effector T-cell activity and produce interferon (IFN-)alpha/beta. In this report we show evidence suggesting that interleukin 2 (IL-2) may play a role in this IFN-alpha/beta production by alloantigen-stimulated BM cells. Alloantigen-induced IFN production by bone marrow cells was completely inhibited when cultures were supplemented with antisera to IL-2. Cell-free supernatants obtained at 2 days from cultures containing C57BL/6 BM cells and irradiated DBA/2J spleen cells were also shown to contain low levels of IL-2 activity and induced significant IFN production in fresh BM cells. Different IL-2 preparations were tested for their ability to induce IFN-alpha/beta production in mouse BM cells. Mouse BM cells cultured with recombinant human IL-2 or highly purified mouse IL-2 produced high levels of IFN-alpha/beta activity after 2-3 days of culture with significant IFN activity being detected as early as 24 hr of culture. IL-2-induced IFN-alpha/beta production was partially resistant to irradiation. In contrast, irradiated (2000 rad) bone marrow cells failed to produce any IFN when cultured with alloantigen in the absence of IL-2. T-cell-depleted BM cells or BM cells obtained from C57BL/10 nude mice produced high levels of IFN-alpha/beta following stimulation with IL-2. In addition, bone marrow cells depleted of Ia+, Qa 5+, or Asialo GM+1 cells produced IFN in response to IL-2. Thus, neither T cells nor NK cells are required for IL-2-induced IFN-alpha/beta production by BM cells. The action of IL-2 on bone marrow cells to induce IFN production was mediated by the classical IL-2 receptor, since monoclonal antibodies to the IL-2 receptor present on T cells blocked this response and since bone marrow cells depleted of IL-2 receptor-bearing cells failed to produce IFN when cultured with IL-2. These results suggest that non-T cells resident in the BM have receptors for IL-2 and can produce IFN-alpha/beta upon stimulation by IL-2. Since IFN has been shown to affect different aspects of hematopoiesis, the production of IFN by BM cells stimulated by IL-2 may be important in the control of hematopoiesis. In addition, IL-2-induced IFN production may play a role in graft-versus-host disease.
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PMID:Interleukin 2 induces interferon alpha/beta production in mouse bone marrow cells. 310 59

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.
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PMID:Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma. 312 92

Cord blood mononuclear cells (MNC) were isolated from 20 normal full-term newborns. These MNC were preincubated with either 50, 100, or 200 micrograms/ml Thymostimulin or without Thymostimulin. The interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production, cytotoxicity, and lymphoproliferation and IL-2 receptor (Tac) expression were all significantly increased after Thymostimulin treatment. For evaluation of the in vivo effect, two combined-immunodeficiency patients defective on the thymic level, one with progressive BCG infection, and one with DiGeorge syndrome were used. Before Thymostimulin treatment, the patient's MNC did not produce sufficient amounts of IL-2 and gamma-IFN. The cytotoxicity and lymphoproliferation were also low. After Thymostimulin treatment, the IL-2 and gamma-IFN production, cytotoxicity, and lymphoproliferative response were enhanced. These results suggest that Thymostimulin may be beneficial in the clinical treatment of primary cellular immunodeficiency. The improved immune reactivity including cytotoxicity and enhanced IL-2 and gamma-IFN production in the Thymostimulin treatment also indicates that there may be a beneficial effect on the combination of chemotherapy and Thymostimulin.
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PMID:Enhancement of interleukin-2 and gamma-interferon production in vitro on cord blood lymphocytes and in vivo on primary cellular immunodeficiency patients with thymic extract (thymostimulin). 313 84

The heavy metals Pb, Ni and Zn have previously been demonstrated to stimulate the proliferation of an Lyt1+2-, L3T4+T-cell. This proliferation required the presence of Ia+ cells and was blocked by monoclonal antibodies directed against self I-A, self I-E and L3T4a. The work reported here examined the role of T-cell factors (IL-2 and gamma-IFN) and their receptors in the metal-induced lymphoproliferation. The metals Pb, Ni and Zn, at concentrations (100 microM) which stimulate T-cell proliferation, had little effect on the ability of the IL-2-dependent cell line HT-2 to respond to exogenous IL-2. This suggests that Pb, Ni and Zn do not modulate the ability of IL-2 to interact with the IL-2 receptor. Ni and Zn significantly enhanced the synthesis/secretion of IL-2 by cultured splenocytes and the expression of the receptor for IL-2; however, Pb produced only slight enhancement. Likewise, anti-IL-2 receptor (7D4) antibodies were able to inhibit a significant portion of the Ni- and Zn-, but not Pb-, induced lymphoproliferation. The residual 3H-thymidine incorporation observed in the presence of anti-IL-2 and anti-IL-2R may represent cycling B-cells induced to proliferate by activated, but non-cyclin, T-cells. Monoclonal anti-gamma-IFN (R4/6A2) equally inhibited all metal-induced lymphoproliferation, suggesting that metal-induced lymphoproliferation is dependent on the induction of gamma-IFN as well as IL-2 synthesis. The Pb-induced response being the least dependent on IL-2 lends support to the hypothesis that Pb, Ni and Zn may activate T-cells and/or B-cells by different mechanisms.
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PMID:The effect of metals on IL-2-related lymphocyte proliferation. 326 42

The neuropeptide arginine vasopressin (AVP) can replace the cytokine interleukin 2 (IL-2) as a T-cell mitogen for the induction of interferon gamma (IFN gamma) expression in splenic cultures. IL-2-like and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. Regulatory functions for IL-2 in the CNS have been suggested. In addition to the spleen, AVP might also mediate some IL-2 effects centrally. In the present study, we evaluated the effect of IL-2 on the in vitro release of AVP from the hypothalamus and amygdala. In addition, we used these release systems to study the possible involvement of NO-mediated signaling in AVP release, based on the reported detection of nitric oxide synthase (NOS) in the hypothalamus and amygdala. IL-2 rapidly stimulates AVP release in both regions, in a calcium- and dose-dependent manner. In addition, nitroprusside also induces AVP release. Norepinephrine also induces AVP release from both the hypothalamus, as well as the amygdala. The norepinephrine-induced AVP release is antagonized by phentolamine, but not by propranolol, suggesting an alpha-adrenergic receptor-mediated AVP response in both brain regions. The IL-2- and acetylcholine-induced AVP release is antagonized by Ng-methyl-L-arginine, indicating a role for NO in this AVP release. Ng-methyl-L-arginine does not affect the norepinephrine-induced AVP release. A stimulatory effect of IL-2 on hypothalamic CRF release and plasma ACTH has already been reported. Our results suggest that in addition to CRF, AVP may also mediate the IL-2 stimulation of ACTH secretion. These data further suggest that in addition to the hypothalamus, the amygdala may also play a role in the bidirectional communication between neuroendocrine and immune systems. Understanding the mode of interaction between IL-2 with AVP could clarify the pathophysiologic or toxic effects of high brain levels of IL-2.
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PMID:IL-2 induces vasopressin release from the hypothalamus and the amygdala: role of nitric oxide-mediated signaling. 752 33

The functional necessity for two CD28 counterreceptors (B7-1 and B7-2) is presently unknown. B7-1 and B7-2 equivalently costimulate IL-2 and interferon-gamma (IFN gamma) production and IL-2 receptor alpha and gamma chain expression. B7-2 induces significantly more IL-4 production than B7-1, with the greatest difference seen in naive T cells. Repetitive costimulation of CD4+ CD45RA+ T cells with B7-2 results in moderate levels of both IL-4 and IL-2, whereas repetitive costimulation with B7-1 results in high levels of IL-2 and low levels of IL-4. Therefore, B7-1 and B7-2 costimulation mediate distinct outcomes, since B7-2 provides an initial signal to induce naive T cells to become IL-4 producers, thereby directing the immune response more towards Th0/Th2, whereas B7-1 is a more neutral differentiative signal.
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PMID:B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. 753 42

Elevated serum levels of soluble tumour necrosis factor receptor (sTNFR-55) and (at a lesser degree) of sTNFR-75 were found in most of the patients with metastatic renal cell carcinoma (RCC) or malignant melanoma (MM) before immunotherapy and with further increase during treatment (intravenous infusions of interleukin-2 [IL-2] and subcutaneous interferon-alpha [IFN-alpha]). In the majority of the patients with MM the pretreatment serum levels of IL-2 and soluble IL-2 receptor (sIL-2R) were increased, whereas fewer patients with RCC presented with increased serum levels of IL-2 and sIL-2R. Twelve days' treatment with IL-2/IFN-alpha, with a rest on days 6 and 7, resulted in a consistent further increase in the serum levels of sIL-2R and sTNFRs. In most patients the increase of sIL-2R and sTNFRs lasted for at least 3 weeks after treatment discontinuation. The clinical significance of the increase remains unknown.
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PMID:Serum levels of cytokines and soluble cytokine receptors in patients with metastatic renal cell carcinoma or malignant melanoma receiving IL-2/interferon-alpha combination therapy. 754 24


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