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 production of interleukin 1 (IL-1) and interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMC) stimulated with human myelin basic protein (MBP) was assessed in vitro in multiple sclerosis (MS) patients in relapse, patients with other neurological diseases (OND) and healthy subjects. Myelin basic protein significantly increased both IL-1 and IL-2 production by PBMC from MS patients during relapse when compared to OND patients or healthy controls. The most efficient concentration of MBP for the induction of IL-1 and IL-2 was 50 micrograms/ml. The optimal IL-1 production occurred after 48 h of PBMC culture and optimal IL-2 production after 72 h of PBMC culture. Anti-Tac monoclonal antibody (MoAb) was used to study IL-2 receptor expression on the same sample of PBM used for IL-2 study in MS patients in relapse. In addition IL-2 receptor expression was studied in PBMC from chronic progressive MS patients. In both MS groups IL-2 receptor expression on PBMC stimulated with MBP appeared higher than in control groups, but these differences were not statistically significant. IL-2 receptor expression on cerebrospinal fluid lymphocytes (CSF-L) either unstimulated or MBP-stimulated was, however, significantly higher in both MS groups when compared to OND patients. These results confirm the presence of activated lymphocytes in the CSF of MS patients during active stages of disease and suggest that this activation may be related to expansion of MBP specific cells.
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PMID:Multiple sclerosis: effect of myelin basic protein on interleukin 1, interleukin 2 production and interleukin 2 receptor expression in vitro. 245 71

The activation of resting T cells to interleukin 2 (IL-2) production and DNA synthesis via Ti-CD3 is dependent on accessory cells (AC). Using positively selected, resting T cells activated with particle-bound anti-CD3, we investigated the ability of various cell lines to function as AC. We found that cell lines able to act as AC all expressed LFA-3, while cell lines not expressing LFA-3 were unable to provide AC signals. This applied to CD3+, CD4+, and CD8+ T cells. Sheep red blood cells (SRBC), which express LFA-3-like molecules, also had a weak, but significant AC function in this test system. Both CD4+ and CD8+ T cells activated with particle-bound anti-CD3 could be induced to enter DNA synthesis in the absence of AC when monoclonal antibodies reacting with CD2 were present instead of AC. IL-2 production could be detected in the latter cultures but not when positively selected CD3+ or CD2+ T cells were cultured alone. Our data suggest that activation of resting T cells via CD3 will lead to IL-2 receptor expression, while the interactions between LFA-3 and its ligand CD2 provide the necessary secondary signals for IL-2 production and induction of DNA synthesis.
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PMID:Accessory cell-dependent T-cell activation via Ti-CD3. Involvement of CD2-LFA-3 interactions. 246 80

The human high-affinity receptor for interleukin 2 (IL-2) has been proposed as being a membrane complex composed of at least two distinct polypeptide chains: p55 (alpha chain), recognized by the anti-Tac monoclonal antibody (mAb), and p75 (beta chain), both of which are capable of binding IL-2. Whereas the alpha chain itself has been shown to be nonfunctional, the beta chain appears to be pivotal in the IL-2 signal transduction, although the beta chain is otherwise poorly characterized. Three beta chain-specific mAbs, designated Mik-beta 1, -beta 2, and -beta 3, were developed. Mik-beta 1 and -beta 2 completely inhibited the IL-2 binding to the beta chain, whereas Mik-beta 3 immunoprecipitated the beta chain crosslinked with 125I-labeled IL-2. The beta chain immunoprecipitated by these mAbs was revealed to have a Mr of 68,000-72,000. High-affinity IL-2 binding was completely abolished by Mik-beta 1. Although IL-2-dependent T-cell growth at high IL-2 concentrations was not inhibited by the anti-Tac, it was almost completely inhibited by Mik-beta 1 in the presence of the anti-Tac. These results clearly indicate that the beta chain is an indispensable component to the high-affinity IL-2 receptor and is responsible for the IL-2 signal transduction. The beta chain was found to be constitutively expressed without the alpha chain on the surface of peripheral blood Leu-19+ natural killer cells.
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PMID:Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. 246 93

The monoclonal antibody (mAb) AHT-107 recognized a determinant distal to the interleukin 2 (IL-2) binding site on the p55 subunit of the IL-2 receptor (IL-2R) (the Tac antigen, CD25) of human T lymphoblasts, while the mAb AHT-54 recognized a determinant close to the IL-2 binding site as did the anti-Tac. The AHT-107 inhibited IL-2 dependent proliferation of human T lymphoblasts equally as well as did the AHT-54. Both mAbs inhibited the high-affinity binding and crosslinking of IL-2 to the p55 + p75 heterodimeric complex on forskolin-treated YT cells. Remarkably, the AHT-107 did not inhibit the low-affinity binding and cross-linking of IL-2 to the p55 molecule on human p55 cDNA-transfected cells, while the AHT-54 as well as anti-Tac did so. In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells. Further, we showed that the AHT-107 did not dissociate IL-2 from the high-affinity IL-2R complex once formed on human T lymphoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on the formation of high-affinity IL-2 binding sites of an IL-2 receptor p55 + p75 heterodimeric complex: functional importance of a determinant on the p55 subunit defined by a monoclonal antibody AHT-107. 246 50

We have identified a suppressive element in the upstream region of the interleukin 2 (IL-2) receptor L chain (Tac) promoter. The inhibitory activity of this element was retained in human T cell leukemia virus type-1 (HTLV-1)-infected T cell lines which express constitutively a large number of IL-2 receptors on the cell surface. The promoter activities of the IL-2 receptor gene did not always correlate with the strong expression of the receptor and its mRNA in the HTLV-1-infected T cell lines we analysed. The results indicate that the constitutive up-regulation of the IL-2 receptor in HTLV-1-infected T cells may be ascribed to not only the transcriptional but also post-transcriptional regulation.
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PMID:Transcriptional regulation alone does not explain the constitutive expression of the interleukin 2 receptor (Tac/L-chain) in HTLV-1 infected cells. 246 52

The human Fc fragment of IgG, when added to blood mononuclear cells in vitro, induces B cell differentiation after 6 days of culture. This activity requires the presence of T cells and monocytes. This work explores the roles of interleukin 1 (IL-1) and interleukin 2 (IL-2) in B cell differentiation induced by Fc fragments. Peripheral blood mononuclear cells (PBMC) from normal donors were examined for plasma cell differentiation following stimulation with Fc fragment (15 and 30 micrograms/ml) with or without IL-1 (6 U/ml) or IL-2 (2 U/ml). Results indicate that both IL-1 and IL-2 accelerated B cell differentiation by the Fc fragment to 3 days of culture, compared to 6 days required with the Fc fragment alone. The time required for differentiation was not further shortened when both IL-1 and IL-2 were present in culture; both IL-1 and IL-2 were able to partially induce B differentiation alone at 6 days of culture. The importance of IL-2 in B cell differentiation was further supported by the finding that antibodies specific for the IL-2 receptor blocked B cell differentiation induced by Fc fragments, with or without additional IL-1 or IL-2. The depletion of monocytes also blocked B cell differentiation and the requirement for monocytes could not be replaced by exogenous IL-1; however, Fc fragments were shown to induce monocytes to secrete IL-1 beta after 24 hr in culture. These results suggest that accelerated differentiation of B cells into plasma cells requires a double signal provided by Fc fragments and IL-1 or IL-2. Monocytes are necessary for Fc fragment-induced differentiation and cannot be replaced by either IL-1 or IL-2.
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PMID:Human B cell differentiation by Fc fragment. III. Effect of IL-1 and IL-2 on differentiation of human B lymphocytes induced by Fc fragments of human IgG. 247 22

Adjuvant arthritis in rats is a T-cell dependent "autoimmune" disease with close similarities to several forms of human arthritis. Injection of mycobacterial adjuvant leads to T-cell activation and proliferation, processes in which the de novo expression of the interleukin 2 (IL-2) receptor plays a pivotal role. The subsequent massive mononuclear cell infiltration of the joints ultimately results in complete joint destruction. Because activation of the helper/inducer subset of T lymphocytes is critical to the establishment of disease, we reasoned that IL2-PE40, a cytotoxic IL-2-Pseudomonas exotoxin fusion protein that targets the membrane-penetration and ADP-ribosylation domains of the toxin to cells bearing the IL-2 receptor, would be an effective and specific therapy. Adjuvant-injected rats were randomized to treatment with IL2-PE40, phosphate-buffered saline, or either of two control proteins related to IL2-PE40 but lacking either the receptor-binding moiety or an enzymatically active toxin domain and previously demonstrated to lack cytotoxicity in vitro. Intraperitoneal IL2-PE40 given before the establishment of overt clinical disease proved an effective and specific modifier of adjuvant arthritis by clinical, histological, and radiographic criteria. Our data suggest that IL2-PE40 may be effective in those diseases in which activated T-cells play an important role.
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PMID:Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats. 249 2

We have used the technique of in situ hybridization to investigate the expression of lymphokine genes by immature thymocytes during intrathymic development. In 13-day fetal thymocytes a population of cells constitutively produces low levels of interleukin 2 (IL-2) and interleukin 4 (IL-4) mRNAs. A second phase of lymphokine gene expression occurs in the majority of 15-day thymocytes, and a population of cells constitutively produces both IL-2 and IL-4 mRNAs. Thymocytes at 14 days of gestation and after 16 days up until birth do not express detectable lymphokine mRNA. By contrast, the population of IL-2 receptor mRNA-producing thymocytes increases progressively up to 15 days of gestation, and expression thereafter decreases up to birth. In addition, thymocytes expressing interferon gamma mRNA were not present until just prior to birth. Our findings indicate developmental control of lymphokine and lymphokine receptor gene expression in fetal thymocytes during ontogeny.
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PMID:Developmental control of lymphokine gene expression in fetal thymocytes during T-cell ontogeny. 249 64

High plasma titers of thyroid and adrenocorticoid hormones are present during the metamorphosis of Xenopus laevis. Here we examine the influence of thyroid hormones on several features of immune reactivity during this period, e.g., the capacity of thymus-derived immunocytes to reduce (immune suppression) or amplify (helper function) antibody production. Further, we test whether thyroid hormone is able to modulate the expression of putative interleukin 2 (IL-2) receptors on lectin-activated adult Xenopus splenocytes, an aspect of helper function. Finally, we have tested the ability of thyroid hormones to affect larval antibody-producing cells directly. Our data suggest that all three functions (suppressor, helper, and antibody producing) are independent of thyroid function during metamorphosis. However, the anatomical distribution of two features of immune suppression, as well as the numbers of lectin-activated splenocytes able to bind anti-IL-2 receptor antibody, were changed by thyroid function. In vivo thyroid blockade by thiourea prevented the transition from the premetamorphic to the adult pattern of distribution of the two suppressor functions; triiodothyronine in vitro stimulated an increase in the numbers of cells able to bind an IL-2 receptor antibody.
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PMID:Thyroid function and immune reactivity during metamorphosis in Xenopus laevis, the South African clawed toad. 253 64

The effect of dexamethasone (Dex) on the differentiation of pokeweed mitogen (PWM), or Staphylococcus aureus Cowan I (SAC)-stimulated human peripheral blood mononuclear cells (PBMC), into immunoglobulin secreting cells (ISC) was studied with special emphasis on the regulatory role of IL-2 in these systems. Dex, known to reduce endogenous IL-2 production and expression of IL-2 receptors, reduced the proliferation of pokeweed mitogen-activated T-cells, and the proliferation was restored by exogenous recombinant interleukin 2 (rIL-2). Furthermore, Dex enhanced in PWM and in SAC-stimulated cultures, the number of ISC. Addition of rIL-2 resulted in a further increase of ISC in SAC-stimulated cultures, whereas in PWM-stimulated cultures the enhancing effect of Dex was reversed. When IL-2 receptors were blocked by a monoclonal anti-IL-2 receptor antibody rIL-2 was no longer suppressive. Addition of monocytes to PWM-stimulated cultures resulted in suppression or the number of ISC, which was even more pronounced when monocytes were pretreated with rIL-2. In contrast to ISC, neither a suppressive effect of rIL-2 nor an enhancing effect of Dex was observed when PWM-stimulated cultures were evaluated for cells with intracytoplasmic immunoglobulin (plasma cells). From these results we conclude that Dex, by blocking IL-2 production and receptor expression, interferes with IL-2 mediated induction and/or activation of suppressor mechanisms.
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PMID:Effect of dexamethasone on mechanisms responsible for regulation of polyclonal B-cell response. 253 83


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