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)

We have analyzed activation of resting human T cells by anti-T cell receptor (TCR) monoclonal antibody (mAb) BMA031, a murine mAb of the G2b isotype. Human peripheral blood lymphocytes (PBL) respond to anti-TCR mAb by short-term proliferation in vitro and by acquisition of responsiveness to interleukin 2 (rIL-2) in the absence of detectable IL-2 production. Cell depletion and limiting dilution experiments indicate that anti-TCR mAb +/- rIL-2 stimulation covers a substantial portion of human T cells, including CD4+ and CD8+ cells. Enhancement by rIL-2 of anti-TCR mAb-induced proliferation is blocked by anti-IL-2 receptor (IL-2R, p55) mAb, while anti-TCR mAb-induced proliferation is not. In contrast, anti-TCR mAb-induced proliferation is blocked by anti-lymphocyte function antigen 1 (LFA-1, CD11a) mAb and is not demonstrable in PBL from two patients with severe congenital LFA-1 deficiency, not even in the presence of irradiated LFA-1+ PBL. We conclude that stimulation of resting human T cells by anti-TCR mAb BMA031 enables dissociation of distinct steps in T cell activation that specifically require participation of IL-2R (p55) and LFA-1 cell surface molecules in a mutually exclusive way.
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PMID:Stimulation of human T cells via anti-T cell receptor monoclonal antibody BMA031: distinct cellular events involving interleukin-2 receptor and lymphocyte function antigen 1. 191 34

Subcutaneous injection of human recombinant interleukin 1 (IL-1) beta was given to 9 patients with urological malignancies (5 renal cell carcinoma, 2 bladder carcinoma, 1 renal pelvic tumor, and 1 testicular tumor), at an initial dose of 1 x 10(4) units on days 1 and 2, and there after weekly for 4 weeks. The dose was increased by 1 x 10(4) units weekly up to final dose of 4 x 10(4) units. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in week 2 and week 4, and lymphokine-activated killer (LAK) activity against Daudi cells was measured using 4 hr 51Cr-release assay, after incubation with human recombinant interleukin 2 (IL-2) of 50 units/ml for 72 hours. Proliferation of lymphocytes was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 hours. IL-1 beta increased the number of peripheral blood granulocytes and lymphocytes, but did not increase the numbers of monocytes and platelets. IL-1 beta significantly augmented IL-2-induced LAK activity in vitro, but this augmentation was neither accompanied by the increase of IL-2 receptor-positive cell ratio in peripheral blood lymphocytes nor enhancement of IL-2-induced proliferation of lymphocytes. Administration of IL-1 beta increased LAK activity of the patients, despite the fact that IL-1 beta did not increase LAK activity in vitro. The result suggests that IL-1 beta-stimulated LAK activity may be mediated by the induction of some cytokines in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of recombinant interleukin 1 beta on peripheral blood cells and induction of lymphokine-activated killer activity in patients with urological malignancies]. 192 Oct 14

Patients with primary intracranial tumors (gliomas) exhibit a profound decrease in immunity, the mechanism of which has, until recently, remained obscure. Here Thomas Roszman, Lucinda Elliott and William Brooks reveal that T cells obtained from these patients exhibit defects in interleukin 2 secretion and in expression of the high-affinity IL-2 receptor and they discuss the role played by immunosuppressive factors produced by gliomas in inducing these defects.
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PMID:Modulation of T-cell function by gliomas. 158 Sep 96

Previously, using flow cytometric resonance energy transfer and lateral diffusion measurements, we demonstrated that a 95-kDa protein identified by two monoclonal antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95-kDa protein (p95) was purified and amino acid sequence data were obtained that showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1). The identity of the p95 protein with ICAM-1 was confirmed by sequential immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells. In functional studies, the antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However, these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent T-cell line. Taken together with our previous observations, the present studies suggest that ICAM-1 is in proximity and interacts physically with the high-affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2 receptors by augmenting homotypic T-T-cell interaction, by receptor-directed focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the physically linked cells to the site of lymphocyte function-associated antigen 1-ICAM-1-IL-2 receptor interaction.
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PMID:Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor. 197 56

Addition of interleukin 2 (IL-2) to IL-2-dependent T cells results in tyrosine protein kinase signal transduction events even though the IL-2 receptor alpha and beta chains lack intrinsic enzymatic activity. Here we report that addition of IL-2 to IL-2-dependent human T cells transiently stimulates the specific activity of p56lck, a member of the src family of nonreceptor tyrosine protein kinases expressed at high levels in T lymphocytes. The ability of IL-2 to induce p56lck activation was found to be independent of the capacity of p56lck to associate with either CD4 or CD8. Following IL-2 treatment, p56lck was found to undergo serine/threonine phosphorylation modifications that resulted in altered mobility of the lck gene product on polyacrylamide gels. These observations raise the possibility that p56lck participates in IL-2-mediated signal transduction events in T cells.
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PMID:T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck. 200 Apr 5

Human interleukin 2 (IL-2) analogs with defined amino acid substitutions were used to identify specific residues that interact with the 55-kDa subunit (p55) or alpha chain of the human IL-2 receptor. Analog proteins containing specific substitutions for Lys-35, Arg-38, Phe-42, or Lys-43 were inactive in competitive binding assays for p55. All of these analogs retained substantial competitive binding to the intermediate-affinity p70 subunit (beta chain) of the receptor complex. The analogs varied in ability to interact with the high-affinity p55/p70 receptor. Despite the lack of binding to p55, all analogs exhibited significant biological activity, as assayed on the murine CTLL cell line. The dissociation constants of Arg-38 and Phe-42 analogs for p70 were consistent with intermediate-affinity binding; the Kd values were not significantly affected by the presence of p55 in binding to the high-affinity IL-2 receptor complex. These results confirm the importance of the B alpha-helix in IL-2 as the locus for p55-receptor binding and support a revised model of IL-2-IL-2 receptor interaction.
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PMID:Localization in human interleukin 2 of the binding site to the alpha chain (p55) of the interleukin 2 receptor. 205 47

Stable transformants of the Jurkat T-cell line have been obtained that express either of two distinct forms of the type 1 human immunodeficiency virus nef gene: the nef-1-encoded protein (Nef-1) contains alanine, glycine, and valine at positions 15, 29, and 33, respectively; the protein specified by nef-2 (Nef-2) has threonine, arginine, and alanine at the corresponding positions. When Jurkat cells or their Nef-2-expressing transformants are treated with phorbol 12-myristate 13-acetate (PMA) plus either phytohemagglutinin (PHA) or antibodies against CD3 epsilon, T-cell receptor beta chain, or CD2, there is a prompt increase in interleukin 2 (IL-2) mRNA and intracellular calcium and in the IL-2 receptor alpha chain on the cell surface. Although cells expressing Nef-1 also induce calcium mobilization and the production of IL-2 receptor alpha chain, the formation of IL-2 mRNA is blocked in response to these stimuli. Moreover, Nef-1-expressing cells transfected with a plasmid in which the IL-2 promoter is fused to the chloramphenicol acetyltransferase (CAT) gene fail to induce CAT following treatment with PMA and PHA. By contrast, the parental and Nef-2-containing cells induce CAT normally. Nef-1-expressing cells can produce IL-2 mRNA in response to a combination of PMA and ionomycin, although much less efficiently than the parental Jurkat cells or Nef-2-expressing cells. These findings, and others described herein, suggest that the virally encoded Nef protein interferes with a signal emanating from the T-cell receptor complex that induces IL-2 gene transcription.
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PMID:Expression of the type 1 human immunodeficiency virus Nef protein in T cells prevents antigen receptor-mediated induction of interleukin 2 mRNA. 205 9

Murine T and B lymphocytes can be induced to release soluble interleukin 2 receptors (sIL2R). This receptor is believed to be a truncated form of the p55 chain of the cell membrane-associated receptor. It has been speculated that this receptor may play an immunoregulatory role via competition for IL-2 with the high-affinity (p55/75 heterodimer) IL-2 receptor. Of crucial importance to this hypothesis are both the concentration of the receptor and its affinity of binding for interleukin 2. We report the measurement of the affinity of sIL2R derived from stimulated normal murine splenocytes for IL-2. We also report the quantification of an enzyme linked immunosorbent assay (ELISA) for sIL2R via measurement of the sIL2R concentration in normal murine splenocyte conditioned medium using a radioimmunometric assay and Scatchard analysis. This method of sIL2R quantification is preferable to sIL2R purification and subsequent concentration estimation as used by previous investigators as any purification process risks destruction of some epitopes. Using the above conditioned medium as a standard we have tested supernatants from several cell lines and sera from several different mouse strains for sIL2R. As would be expected this method of quantification yielded a markedly different value for serum sIL2R levels in normal mice than that obtained by previous investigators. Our results indicate that it is very unlikely that sIL2R competes with the high-affinity form of the IL-2 receptor for IL-2. However, it is possible that it competes for IL-2 with the medium-affinity p75 form of the IL-2 receptor and as such is important in restricting unwanted non-specific (bystander) activation of p75 expressing cells. Evidence from both our previous work as well as from the literature is presented to support this hypothesis.
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PMID:A regulatory role for the soluble IL-2 receptor via competition with the p75 cell-surface form of the receptor for IL-2. 208 Sep 85

Dysfunctional monocytes (M phi), exerting their inhibitory functions via prostaglandin E2 (PGE2), have been implicated in the depression of immune responses following major surgical, accidental, and burn trauma. A randomized prospective study of the PG-synthetase inhibitor indomethacin (Indo) was performed in 43 patients undergoing major surgical procedures, to evaluate its efficacy in correcting postoperative abnormalities of the cell-mediated immune system (CMI) and preventing infectious morbidity and mortality. Patients, following gastrectomy (GX) or reconstruction of the abdominal aorta (AG), in the treated group (PIndo), received 100 mg IV of Indo 6 hours postoperatively and 3 x 50 mg IV Indo over 24 hours on postoperative days (D) 1,2,3,4. The rate of infectious complications was recorded. Parameters of CMI evaluated preoperatively (D0) and on D1,D3,D5,D7 were: Delayed type hypersensitivity (DTH) response to recall antigens, mitogen-induced lymphocyte proliferation (LP), interleukin 2 (IL-2) synthesis, and phenotyping of mononuclear blood leukocytes (PBMC's) with the monoclonal antibodies for CD3+, CD4+, IL-2 receptor (IL-2R)+ and LeuM3+ receptor sites. In contrast to the group of untreated patients (Pc), PIndo did not show a depression of their preoperative DTH responses, and they also showed a lower rate of early opportunistic infections. The in vitro test of CMI revealed that there was a higher LP capacity in PBMC's of PIndo (p less than 0.05); the postoperative profile of IL-2 synthesis was not statistically different between the groups. Indomethacin administration resulted in a considerable alleviation of postoperative monocytosis (p less than 0.05) and in a protective effect on lymphocyte receptor expression of CD3+, CD4+, and IL-2R+ cells. From these data it is concluded that in vivo cyclooxygenase inhibition may be useful to prevent impairment of CMI, a crucial predisposing factor of the high susceptibility to postoperative infection.
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PMID:Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma. 210 39

Psoriasis represents inflammatory skin disorders characterized by significant changes in cellular immunity, particularly exhibiting alterations in T lymphocyte-related functions. Early psoriatic lesions have been reported to show an infiltration of activated helper T cells. Elevated levels of interleukin 2 (IL-2), IL-2 receptor (IL-2R), and interferon-gamma (INF-gamma) are associated with an early activation of T cells. To examine local activation of T cells in psoriatic skin, the amounts of activated T cell products, IL-2, secretory form of IL-2R (sIL-2R) and INF-gamma were measured in the fluids of suction blisters raised on psoriatic skin. sIL-2R levels were significantly elevated in the suction blister fluids raised on psoriatic involved skin compared with those on normal and psoriatic uninvolved skin. On the other hand, neither IL-2 or IFN-gamma was detected in the suction blister fluids either from normal, psoriatic uninvolved, or involved skin. However, we could detect IFN-gamma and IL-2 in the psoriatic scale extracts. Although we failed to detect IL-2 and IFN-gamma in the suction blister fluids, the increased levels of sIL-2R in the suction blister fluids from the psoriatic lesional skin indicate local activation of T cells in psoriatic lesional skin.
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PMID:Interleukin 2, soluble interleukin 2 receptor, and interferon-gamma in the suction blister fluids from psoriatic skin. 206 14


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