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 mRNA expression of interleukin (IL)-2, IL-2 receptor-alpha-chain (IL-2R alpha), IL-4 and interferon-gamma (IFN-gamma) in spleen cells from NZB/NZW F1) mice following the stimulation with concanavalin A (Con A) was examined by Northern blot analysis. Kinetic patterns of the mRNA expression after the stimulation were not different between 2-month-old and 6 to 8-month-old B/W F1 mice. However, relative mRNA expression of IL-2 to a cytoskeletal protein, alpha-Tubulin was lower in 6 to 8-month-old B/W F1 mice than in 2-month-old mice. Similar but not significant tendency was observed in IL-2R mRNA expression. In contrast, Relative IL-4 mRNA expression in 6 to 8-month-old B/W F1 mice was significantly higher than that in 2-month-old animals. On the other hand, no apparent change was observed in IFN-gamma mRNA expression. Flow cytometric analysis indicated that there was no apparent difference in proportion of L3T4 positive T cells in spleen cells from 2 and 6 to 8-month-old B/W F1 mice. These results suggest that mRNA expression of IL-2 and IL-4 differentially changes with aging in autoimmune B/W F1 mice.
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PMID:Age-related differential mRNA expression of T cell cytokines in NZB/NZW F1 mice. 765 92

Interleukin 2 (IL-2) is one of the major cytokines produced by T lymphocytes in response to antigen. It is a potent growth and differentiation factor for several cell-types and is structurally related to the four-helix bundle family of cytokines. Mutation of residue Phe42 to Ala abolishes binding to the alpha chain of the tri-partite IL-2 receptor. The three-dimensional structure of the F42A mutant IL-2 has been calculated by two dimensional NMR methods and compared to a structure of wild-type IL-2 determined by X-ray crystallography. The overall topology of the two structures is the same. The main differences between the structures are within the ill-defined loops connecting the helices and the region of the protein that is believed to interact with the alpha-chain of the receptor. Thus, the mutation of Phe42 to Ala does not perturb the overall three-dimensional structure of IL-2, and does not appear to change the putative binding sites for the beta and gamma chains of the receptor. The structural differences observed in this mutant suggest that the replacement of Phe42 with Ala causes the re-orientation of neighbouring side-chains that are also involved in binding the alpha-chain of the receptor.
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PMID:The solution structure of the F42A mutant of human interleukin 2. 772 44

Recent work has shown that T lymphocytes undergo apoptosis upon treatment with the glucocorticoid analogue dexamethasone. These cells can be protected from the effect of dexamethasone by interleukin-2 (IL-2) or IL-4. We were interested in analysing whether a transfected cell dependent on three different lymphokines could be protected by them from the effect of dexamethasone. In addition, we took advantage of our cellular system, in which we expressed intermediate- or high-affinity IL-2R independently, to analyse the role of these receptors in the protection from glucocorticoid-induced apoptosis. In this report we show that IL-2 rescues murine T cells expressing exogenous intermediate- (TS1 beta) or high-affinity (TS1 alpha beta) IL-2 receptor (IL-2R) from dexamethasone-induced apoptosis. This result suggests that intermediate-affinity IL-2R alone can replace high-affinity IL-2R for the protection from the effect of dexamethasone. In addition, IL-4 and IL-9 are rescue-factors, as well as IL-2, of glucocorticoid-treated TS1 beta and TS1 alpha beta cells. Our data suggest that the presence of the alpha-chain of the IL-2R is not required for rescue by IL-2 from the effect of dexamethasone. In addition, we show that proliferation is not required for preventing glucocorticoid-induced apoptosis. This result implies a new role for the intermediate-affinity IL-2R.
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PMID:A role for the intermediate affinity IL-2R in the protection against glucocorticoid-induced apoptosis. 775 Oct 21

Co-stimulation of highly purified peripheral T lymphocytes from healthy blood donors with the adhesion molecules CD2 and CD28 in association with recombinant interleukin-7 (rIL-7) induced T-cell proliferation, multiple cytokine secretion and IL-2 receptivity. We demonstrated that rIL-7 is as potent as rIL-2 in inducing the proliferation of unseparated, CD4+ and CD8+ T cells. In contrast to low or undetectable levels of IL-1 alpha, IL-6 and IL-2, high levels of tumour necrosis factor-alpha (TNF-alpha), IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were secreted. Experiments using blocking antibodies suggested a direct mechanism for rIL-7 co-stimulatory effect, although induction of the CD25/IL-2 receptor alpha-chain (CD25/IL-2R alpha) was observed. Monoclonal antibodies (mAb) against the adhesion molecules CD2 and CD28 are likely to mimic the interaction with their respective physiological ligands [lymphocyte function-associated antigen-3 (LFA-3)/CD58, CD59 and CD48 for CD2, B7/BB1 for CD28]. Taken together, these in vitro data suggest that IL-7 could participate in paracrine interactions between T lymphocytes and thymic stromal cells or dendritic cells, via its potent co-stimulatory activity with CD2 and CD28 adhesion molecules.
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PMID:Interleukin-7 is a potent co-stimulus of the adhesion pathway involving CD2 and CD28 molecules. 790 90

Human intestinal lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition, T cells in the effector compartment of the mucosa bear surface antigens that are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors, and IL-2 receptor alpha-chain mRNA, and are able to synthesize high amounts of IL-2. However, other markers of memory T cells, as CD29, are not expressed in high density in the lamina propria, indicating that lamina propria T cells differ from "classical" memory T cells. This is supported by functional studies in nonhuman primates infected rectally with Chlamydia trachomatis that show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. These findings indicate a specific state of differentiation of lamina propria T cells that is adapted to the specific requirements in the gut. In inflammatory bowel disease (IBD) and in celiac disease, an increase in the number of CD25-positive activated T cells is found in involved mucosa. It has been shown that mucosal T-cell activation induces epithelial cell damage and mucosal transformation. Thus, a T cell-mediated damage may contribute to the pathogenesis of IBD. HIV-infected patients have a decreased number of CD4-positive T cells in the intestinal lamina propria. The number of CD25-positive activated T cells is also significantly decreased in the intestine compared to controls. Correlating with the presence of HIV-infected mononuclear cells in the mucosa, mucosal atrophy with hyporegeneration and enterocyte dysmaturation is observed. HIV might thus cause impairment and depletion of activated regulatory T cells in the intestinal lamina propria, which could lead not only to a breakdown of the mucosal immune barrier, resulting in a variety of opportunistic infections, but also to malabsorption, due to mucosal atrophy or enterocyte dysfunction. These findings indicate a close relationship between mucosal T cells and enterocyte proliferation and maturation.
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PMID:Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system. 797 5

Soluble proteins of the human immunodeficiency virus (HIV) might play a significant role in the pathogenesis of HIV infection. The addition of synthetic Tat peptides, but not that of the recombinant Nef or Vif protein, inhibited proliferative responses of CD4+ tetanus antigen-specific, exogenous interleukin-2 (IL-2)-independent T-cell clones in a dose-dependent manner. In addition, Tat peptides inhibited the anti-CD3 monoclonal antibody-induced proliferative responses of both purified CD4+ and CD8+ T cells. Tat did not affect proliferative responses induced by phorbol myristate acetate plus ionomycin. The Tat peptides at the concentrations used (0.1 to 3 micrograms/ml) did not affect the viability of the cells as determined by trypan blue exclusion. Treatment of Tat peptides with polyclonal Tat antibodies abrogated the inhibitory effect of Tat. Soluble Tat proteins secreted by HeLa cells transfected with the tat gene also inhibited antigen-induced proliferation of the T-cell clones. Tat inhibited the anti-CD3 monoclonal antibody-induced IL-2 mRNA expression and IL-2 secretion but did not affect IL-2 receptor alpha-chain mRNA or protein expression on peripheral blood T cells. Finally, treatment of T-cell clones with the Tat peptide did not affect the antigen-induced increase in intracellular calcium, hydrolysis of phosphatidyl inositol to inositol trisphosphate, or translocation of protein kinase C from the cytosol to the membrane. These studies demonstrate that the mechanism of the Tat-mediated inhibition of T-cell functions involves a phospholipase C gamma 1-independent pathway.
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PMID:Human immunodeficiency virus Tat induces functional unresponsiveness in T cells. 798 46

Asthma is a multifactorial disease of unknown etiology but often associated with atopy and inflammation. Previous studies in adult asthma have demonstrated the presence of activated T cells in blood, bronchoalveolar lavage (BAL) fluid, and bronchial tissue, and the relevance of their soluble products for eosinophil function. In view of these observations, it was hypothesized that similar pathogenetic mechanisms also occur in childhood asthma. In fact, peripheral blood T lymphocytes in 14 children with house-dust mite allergic asthma showed clear evidence of T cell activation as measured by the expression of CD25 and HLA-DR antigen. Without changing medication, significant reduction of the IL-2 receptor alpha-chain expression within the CD4+ lymphocyte population was observed after only 3 weeks of allergen avoidance. Within this time period, absolute and relative eosinophil numbers decreased to normal levels. After 5 weeks in an area of low house-dust mite exposure, lung function also presented evidence for clinical improvement of the asthmatic disease. These results indicate similar pathogenetic mechanisms in childhood and adult asthma. Furthermore, they suggest that allergen avoidance may contribute to the efficient therapy of asthma in patients with house-dust mite IgE-meditated allergy.
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PMID:High altitude climate therapy reduces peripheral blood T lymphocyte activation, eosinophilia, and bronchial obstruction in children with house-dust mite allergic asthma. 805 24

DAB486IL-2 is a recombinant toxin with the cell surface-binding domain of diphtheria toxin (DT) replaced by interleukin-2 (IL-2). To correlate clinical response with expression of components of the IL-2 receptor (IL-2R), 14 patients with cutaneous T-cell lymphoma (CTCL) received five daily 90-minute infusions every 21 days. There were no complete responses, 1 partial response (PR), 2 major biologic effects (major cutaneous improvement without change in circulating neoplastic cells), 3 stable disease (SD), and 8 progressive disease (PD). Responders had easily detected expression of CD25 (Tac; alpha-chain of IL-2R) in skin, and in two responders expression of the beta chain of the IL-2 receptor (beta-IL-2R) was detectable by reverse transcriptase-polymerase chain reaction. CD25 was also detected in 8 of 11 SD or PD patients, with beta-IL-2R in 3 of 8 SD or PD patients. Two of the three responders had anti-DT antibodies before treatment. Reversible increased hepatic transaminases occurred in 13 of 14 patients during the first course, with decreased frequency in repeated courses. The maximal serum concentration after the first infusion of DAB486IL-2 varied (1,369 +/- 1,155 ng/mL [mean +/- SD]; n = 14; range, 55 to 3,999 ng/mL) with a short half-life (T1/2 beta = 0.21 +/- 0.12 h [mean +/- SD]; range, 0.099 to 0.57 h). The area under the concentration curve varied inversely with anti-DT antibody titer. We conclude that DA-B486IL-2 has valuable activity in certain patients with CTCL. Expression of the IL-2R may be necessary but is not sufficient to predict response.
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PMID:Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and the Sezary syndrome: correlation of activity and interleukin-2 receptor expression in a phase II study. 808 Sep 84

A transgenic mouse system has been established to follow the pattern of IL-2 expression at the level of single T cells. This was achieved by introducing a human IL-2 promoter-driven reporter gene (Escherichia coli lacZ) into the germline of mice and monitoring its product, beta-galactosidase (beta-gal), by FACS analysis. Ex vivo experiments confirmed that the regulated expression of the transgene is comparable with that of the endogenous IL-2 gene. Transgene expression is inducible by mitogens, restricted to T cells, and diminished by immunosuppressive agents, such as cyclosporin A, at concentrations known to suppress IL-2 transcription. Depending on the mitogens used, 30-50% of peripheral T cells produced IL-2 with an asynchronous induction pattern, as measured by transgenic beta-gal activity. Both helper (CD4+CD8-) and cytotoxic T cells (CD4-CD8+) respond with comparable heterogenous expression levels but they show different frequencies of beta-gal production. Transgenic beta-gal-producing T cells were detectable as early as 2 h after mitogen stimulation. These cells represent a transitional IL-2 secreting, IL-2 receptor alpha-chain negative T cell population, which occurs in the autocrine process of T cell activation. Administration of staphylococcal enterotoxin A (SEA), a bacterial superantigen, resulted in a T cell specific (Thy-1.2) increase (2.5-fold) of reporter gene expression in vivo. In summary, we could demonstrate that IL-2 promoter-driven reporter gene expression in transgenic mice is a sensitive tool to characterize IL-2 expressing cells phenotypically.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-2 promoter-driven lacZ expression as a monitoring tool for IL-2 expression in primary T cells of transgenic mice. 815 96

Adult T cell leukemia-derived factor (ADF), originally defined as an IL-2 receptor alpha-chain (IL-2R alpha)/p55 (Tac) inducer, is a human thioredoxin homologue and has many cytokine-like activities. In this study, we examined the regulatory effect of ADF on eosinophil migration using human eosinophils and an eosinophilic subline of HL-60 human promyelocytic leukemia cells, YY-1. rADF induced migration of eosinophils from patients with hypereosinophilia, although rADF exhibited little activity on eosinophils from healthy donors. When human eosinophils were incubated with rADF (0.1-10 micrograms/ml) at 37 degrees C for 24 h, both chemotactic and chemokinetic activity of the complement anaphylatoxin peptide C5a on eosinophil migration was markedly enhanced in a dose-dependent manner. Similarly, this enhancing effect of rADF was observed in the migration assay using YY-1 cells. In contrast, rADF showed no modulation of migratory behavior of human eosinophils and YY-1 cells by IL-3, IL-5, nor granulocyte-macrophage colony-stimulating factor. Scatchard analysis of C5a receptors on YY-1 cells using 125I-C5a showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. Furthermore, mutant ADF (mADF), which had no reducing activity, had no enhancing effect on C5a-induced eosinophil migration. These results indicate a possible involvement of ADF in the recruitment of eosinophils through redox regulation by a dithiol reductase activity.
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PMID:Regulation of eosinophil migration by adult T cell leukemia-derived factor. 822 51


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