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)

Interleukin-2 (IL-2) responsiveness of Dermatophagoides farinae (Df)-stimulated lymphocytes from children with bronchial asthma was studied. Six-day culture of lymphocytes from allergic patients increased after an additional 3 days of incubation with recombinant IL-2. This phenomenon was not observed when the lymphocytes of patients allergic to Df were stimulated with ovalbumin (OVA). Normal lymphocytes stimulated with Df expressed Tac antigen (low-affinity IL-2 receptor) but, in contrast to the patients' lymphocytes, did not absorb nor respond to IL-2. Nonadherent responder cells cultured with Df-pulsed autologous adherent cells acquired IL-2 responsiveness, but those cultured with OVA-pulsed adherent cells did not. The monoclonal antibody to HLA-DQ framework (Leu 10 and clonab DQ), but not to HLA-DR framework (OKIa1) and HLA-DP (HLA-DP and clonab DP-DR), blocked the antigen-presenting cells from inducing IL-2 responsiveness. Nonadherent responder cells depleted of OKT4 (CD4)-positive cells failed to acquire IL-2 responsiveness, whereas depletion of OKT8 (CD8) cells had no impact. Taken as a whole, the results indicate that DQ-bearing adherent cells from allergic donors play a key role in presenting Df antigen to allergen-specific responder T cells, which are very likely to be members of the OKT4 positive subset.
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PMID:Allergen-specific induction of interleukin-2 (IL-2) responsiveness in lymphocytes from children with asthma. I. Antigen specificity and initial events of the induction. 247 92

Interleukin-2 (IL-2) plays an essential role in the clonal expansion of antigen-activated T lymphocytes (T cells). In fact, the expression of both IL-2 and IL-2 receptor (IL-2R, p55, CD25) genes is transiently induced upon T cell activation through the interaction of antigen/major histocompatibility complex (MHC) and T cell receptor complex. To elucidate the mechanism(s) of the induced gene expression for IL-2 and IL-2R, we have investigated for the presence of potential transcription factors that specifically interact with regulatory cis-elements. Here, we demonstrate that one such factor mediates the induced expression of both genes. Interestingly, the recognition sequences by this factor are significantly diverse in these two genes and are related to those of immunoglobulin (Ig) kappa chain and MHC class I genes. We provide evidence that this factor indeed binds to the IL-2, IL-2R, and Ig sequence elements with different affinities, thereby affecting the magnitude of gene expression. Interestingly, this factor also binds to other cytokine genes, such as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and HIV-1 and HTLV-1 LTR sequences.
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PMID:Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes. 251 55

Cell-mediated immunological function was studied in 18 patients with dilated cardiomyopathy (DCM) making use of peripheral blood lymphocytes (PBL). The results were as follows: 1) Blastoid transformation of PBL stimulated with phytohemagglutinin (PHA) was significantly suppressed in patients with DCM compared with normal controls (p less than 0.01). 2) The T-cell subset ratio of Leu-3a-positive cells to Leu-2a-positive cells was significantly higher in patients with DCM than that in the control group (p less than 0.05). 3) Interleukin-2 (IL-2) production of PBL under PHA stimulation was enhanced significantly in patients with DCM (p less than 0.05). 4) IL-2 receptor-positive cells were significantly fewer in number in patients with DCM than in controls (p less than 0.05). These results suggest that immunological disorders including changes in the IL-2 system are present in some patients with DCM and may play a role in the occurrence of DCM.
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PMID:Immunological disorders in patients with dilated cardiomyopathy. With special reference to the production of interleukin-2 and the expression of interleukin-2 receptors in the patients' peripheral blood lymphocytes. 263 33

Activated lymphocytes may have potent biologic effects outside the frame of the immune system. In these studies we analyzed the interaction of activated normal human lymphocytes and/or soluble products of lymphocyte activation on the contractile activity of isolated rat atria. The results indicate that phytohemagglutinin activated lymphocytes of the CD4 phenotype exert a positive inotropic effect on spontaneously beating atria. This effect is linked to steps of lymphocyte activation that precede cell division. Soluble factors released to the supernatant of stimulated lymphocytes can substitute for the intact cells. Interleukin-2 (IL-2) appears to be an important component of the active supernatants, as their activity can be reduced by monoclonal anti-IL-2 or by preincubation of the heart tissue with monoclonal anti-IL-2 receptor (anti-Tac). Highly purified IL-2 was active at 10 units/ml. In order to induce a positive inotropic effect at lower doses of natural or recombinant IL-2 (2-3 units/ml), synergic factors were required (2 x 10(-6) M arachidonic acid, AA, or Ca ionophore A 23187). Indirect evidence indicates that IL-2 exerts its biologic effect by turning on the phosphoinositide cycle and activating protein kinase C in the heart tissue target. It is postulated that similar mechanisms may be activated in inflammatory myocardiopathies or during the treatment of cancer with massive doses of IL-2.
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PMID:[The effect of activated lymphocytes on cardiac contractility]. 264 Apr 86

The purposes of this work are to: review the biological activities of Interleukin-2 (IL-2); evaluate the reported therapeutic benefits and toxicity of IL-2/lymphokine activated killer (LAK) cells; and project the role of IL-2/LAK cells in cancer therapy. Interleukin-2 is a glycoprotein lymphokine (mw 15,000) produced naturally by mitogen or antigen stimulated T-lymphocytes. The activities of IL-2 include: enhancement of IL-2 receptor positive T-lymphocytes and a variety of other in vitro and in vivo alterations of T cell function. The IL-2 gene has been cloned from the Jurkat leukemia cell line and expressed by recombinant biotechnology in an E. coli vector. In vitro incubation of IL-2 with selected T-lymphocytes results in the formation of lymphocyte activated killer (LAK) cells. Rosenberg and colleagues, in 1983, demonstrated that both exogenous IL-2 and LAK cells were needed in order to get maximum tumor regression in a murine model and later humans. Patients selected for IL-2/LAK cell therapy have clinical metastases or advanced unresectable cancers. Almost all patients treated demonstrate some toxic effects, including chills, fever, nausea, vomiting, diarrhea and hepatic dysfunction. Approximately 75 percent of the patients have profound hypotension and require intensive nursing care. A review of the literature indicates that tumor responsiveness will range from negligible (adenocarcinoma of the lung with metastases) to a 30+ percent response in renal cell carcinoma when complete and partial responders are totalled. Interleukin-2/LAK cell therapy has promise for some wide spread tumors for which no other therapy is available.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-2 and lymphokine activated killer cells: promises and cautions. 264 90

The current study analyses the ultramorphology, lymphocyte activation marker expression, DNA synthesis, and gamma-interferon and immunoglobulin production of inflammatory cells in oral lichen planus (OLP) lesions. According to these four different aspects of lymphocyte activation, only a minor fraction, 5% at the most, of all T cells in situ were activated. However, it is this minor fraction, and not the resting T cells without signs of activation, which may prove decisive for the outcome of the local immune-inflammatory process in OLP. We also studied both spontaneous and phytohaemagglutinin (PHA) stimulated peripheral blood T cell function. 3H-thymidine incorporation and gamma-interferon secretion were determined. Interleukin-2 (IL-2) receptor and major histocompatibility complex (MHC) locus II coded la antigen were stained with monoclonal antibodies. The peripheral blood T cell subsets and spontaneous MHC locus II antigen expression were similar in OLP patients and healthy controls, whereas spontaneous lymphocyte proliferation was lower in OLP patients (p less than 0.01). The PHA induced expression of IL-2 receptor and T cell proliferation were similar in both groups. Gamma-interferon secretion and MHC locus II antigen expression were low in OLP patients compared with the controls (p less than 0.01). The results suggest a defect in OLP T cell activation disclosed by in vitro PHA stimulation and occurring between IL-2 receptor ligand binding and gamma-interferon secretion. The findings of our peripheral blood mononuclear studies do not, however, provide an easy or straightforward explanation of the changes observed in the disease itself, particularly with respect to local pathogenesis.
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PMID:Lymphocyte activation in oral lichen planus. 266 69

Interleukin-2 (IL-2) stimulated H-thymidine incorporation in the blasts of six of 21 cases of acute myeloid leukaemia (AML). An IL-2 induced increase in cell numbers was directly demonstrated in the two patients studied in this way, and T-cell contamination was rigorously excluded. The IL-2-induced proliferation was usually less marked than that caused by granulocyte-macrophage colony stimulating factor (GM-CSF), and IL-2 moderately enhanced GM-CSF-induced stimulation in five of the six patients; in the sixth, IL-2 and GM-CSF were strongly synergistic. IL-2-induced proliferation was observed only in AML with a monocytic component (M4/M5), but not all M4/M5 leukaemias responded to IL-2. There was no correlation between expression of the light-chain of the IL-2 receptor and IL-2-induced stimulation. It is suggested that IL-2 is involved at a restricted stage of early myelopoiesis, perhaps when cells are becoming committed to the monocytic lineage; and that IL-2 is a growth factor for early myeloid cells in a proportion of cases of AML.
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PMID:IL-2 and myelopoiesis: IL-2 induces blast cell proliferation in some cases of acute myeloid leukaemia. 268 57

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.
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PMID:Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. 278 15

We previously reported that alveolar lymphocytes in patients with active sarcoidosis are sensitized to Propionibacterium acnes (P. acnes) which may play a significant role in the induction of alveolitis in these patients. However, the mechanism of lymphocyte activation is not fully understood. In this study, we further investigated the production of Interleukin-2 (IL-2), and the responsiveness to IL-2 of alveolar lymphocytes obtained from sarcoidosis patients and stimulated by P. acnes in vitro. In 21 untreated sarcoidosis patients, 7 treated patients and 13 control subjects, the mean IL-2 activity of fluid released from cultured alveolar lymphocytes was 9.8 +/- 15.7 u/ml (M +/- SD), 1.9 +/- 4.7 u/ml and 0.2 +/- 0.8 u/ml respectively. The IL-2 activity of lymphocytes from untreated patients was significantly higher than that of control subjects (p less than 0.02). The responsiveness of alveolar lymphocytes to recombinant IL-2 was evaluated by 3H-thymidine uptake in the presence and absence of P. acnes. Lymphocytes stimulated by P. acnes showed a significantly increased uptake (3766 +/- 3929 dpm) compared to unstimulated lymphocytes (1123 +/- 968 dpm) obtained from 11 untreated sarcoidosis patients (p less than 0.02). On the other hand, the responsiveness of lymphocytes obtained from 6 control subjects was low, regardless of stimulation by P. acnes. There was a significant correlation (p less than 0.05) between the P. acnes-induced production of IL-2 by alveolar lymphocytes and the blastogenesis of alveolar lymphocytes in untreated sarcoidosis patients. Our data indicate that P. acnes stimulates IL-2 production and IL-2 receptor induction in alveolar lymphocytes from patients with active sarcoidosis.
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PMID:[Interleukin-2 production and receptor expression of alveolar lymphocytes stimulated by Propionibacterium acnes in sarcoidosis]. 278 41

The biological activity of recombinant Interleukin-2 (rIL-2) administered intraperitoneally (ip) has not been determined and may differ significantly from the maximum tolerated dose (MTD). In this trial, the pharmacokinetics, toxicity, and biologic activity of a single ip dose were studied initially followed a week later by a 5-day ip rIL-2 given for 2 weeks every 28 days. Planned dose escalation was from 2 x 10(3) to 2 x 10(7) U given in 2 liters of D5W. Drug was obtained from the NCI and was administered through an ip port. Four patients received 1 U/ml and four patients received 10 U/ml. Preliminary data demonstrate an increase in the peritoneal fluid mononuclear cell count. Mononuclear cell phenotyping tested in the first eight patients showed a modest increase in Leu 2a+, Leu 15- cells, corresponding to CTL. A similar increase in Leu 19+ cells was also demonstrated (NK cells). Soluble IL-2 receptor was elevated in peritoneal fluid. Cytotoxicity against K562 and Daudi cell lines was not observed at the first two dose levels. Toxicity of treatment was minimal and related to abdominal distention. No objective responses were seen but in one patient we documented a reduction in serum CA-125 levels. The observed biologic response and lack of toxicity is promising and justifies further exploration of this immune-modulating approach.
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PMID:Phase IB study of low-dose intraperitoneal recombinant interleukin-2 in patients with refractory advanced ovarian cancer: rationale and preliminary report. 278 2


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