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 cytochalasans, fungal metabolites that interact with actin, can affect lymphocyte proliferation; high concentrations inhibit lectin-induced proliferation and low concentrations augment it. The phorbol ester tumor promoter, PMA, alone is not mitogenic for primary lymphocytes but enhances the activity of mitogenic lectins. Because the cytochalasans have been reported to increase intracellular Ca2+ and because PMA activates protein kinase C, lymphocytes were treated with PMA and cytochalasin B (CyB) to determine if this combination would induce DNA synthesis. While this treatment by itself did not cause proliferation, lymphocytes cultured with PMA and CyB overnight, washed, and recultured with IL-2 proliferated to the same degree as lymphocytes stimulated with Con A. Three different cytochalasans, cytochalasin B, cytochalasin D, and chaetoglobosin C, all of which bind to cellular actin with different affinities and only one of which affects glucose transport, induced IL-2 receptors in combination with PMA. Flow cytometric analysis with an antibody to the IL-2 receptor alpha subunit confirmed the induction of receptors on CD8+ cells. However, no IL-2 was produced after the exposure of lymphocytes to the combination of cytochalasans and PMA. Therefore, there was sufficient signal to induce IL-2 receptor expression but not to induce IL-2.
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PMID:Cytochalasans and PMA induce IL-2 receptors on CD8+ lymphocytes. 139 84

Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.
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PMID:Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection. 143 Jan 8

We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8+ TAL, the presence of TNF alpha was associated with a selective increase in CD8+ IL-2R+ (Tac+) cells, and subsequent decrease in CD4+ IL-2R+ (Tac+) cells. These results suggest that the observed facilitation of the outgrowth of CD8+ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF alpha in the analysis of signalling in autologous tumor-reactive CTL.
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PMID:Induction of interleukin-2 receptor by tumor necrosis factor alpha on cultured ovarian tumor-associated lymphocytes. 153 15

(6R)-5,6,7,8-Tetrahydrobiopterin is produced by stimulated human T lymphocytes, and is known to affect various aspects of interleukin-2-directed T cell proliferation. Using an increased apparent affinity of interleukin 2 receptor to interleukin 2 as a measure of activity, this study explores whether other 6-substituted pterins might have the same effect, and what structural features are necessary for activity. Of the compounds tested, only the T-lymphocyte-derived (6R)-5,6,7,8-tetrahydrobiopterin was active. The diastereomeric (6S)-5,6,7,8-tetrahydrobiopterin was inactive, as were 7,8-dihydrobiopterin, sepiapterin, 5,6,7,8-tetrahydroneopterin, 6,7-dimethyl-5,6,7,8-tetrahydropterin and 6-hydroxymethylpterin. 7,8-Dihydroneopterin and neopterin were also found to be inactive. It follows that neither of these compounds participates in the feedback modulation of IL-2 receptor affinity, although both of them can be detected upon IFN-gamma stimulation of human monocytes/macrophages. A computer-based molecular modelling study of (6R)-5,6,7,8-tetrahydrobiopterin and (6R)-5,6,7,8-tetrahydroneopterin revealed substantial differences in overall shape between the two molecules, with certain features figuring prominently in the low-energy conformers of (6R)-5,6,7,8-tetrahydrobiopterin.
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PMID:Structural requirements for the modulatory effect of 6-substituted pterins on interleukin 2 receptor binding. 153 94

Mycobacterium avium is an intracellular opportunistic pathogen commonly seen in AIDS patients. M. avium-infected monocytes have been recently shown to be lysed by interleukin-2 (IL-2)-activated killer cells. Since some bacterial products can directly augment natural killer activity, we examined the ability of these microorganisms to induce killer cell activity. Coculture of M. avium with large granular lymphocytes (LGL) was found to augment the ability of LGL to lyse both tumor cells and bacterially infected autologous monocytes. The induction of tumoricidal activity by M. avium was only partially neutralized by the presence of anti-IL-2 antibodies, indicating that both IL-2-dependent and IL-2-independent mechanisms are responsible for activation of killer cells. Furthermore, only the direct interaction between bacterium and LGL could induce the expression of both IL-2 receptor alpha protein and mRNA, an effect which was abrogated by the presence of genistein, a tyrosine kinase inhibitor. Thus, M. avium was seen to induce killer cells, an activity that is concomitant with the up-regulation of IL-2 receptor alpha, or Tac antigen, expression and which involves signal transduction mechanisms mediated by tyrosine kinase activity.
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PMID:Mycobacterial induction of activated killer cells: possible role of tyrosine kinase activity in interleukin-2 receptor alpha expression. 161 49

Resting natural killer (NK) cells express the p75 chain of the IL-2 receptor (IL-2R beta) and most NK cells express the CD2 (erythrocyte rosette) receptor. The cell adhesion molecule, LFA-3, is a natural co-ligand for CD2. Tac antigen (IL-2R alpha), a p55 IL-2R subunit, can be expressed after NK activation and may play a role in IL-2-induced NK proliferation. Little is known of the molecular mechanisms underlying cytokine production in NK cells. We investigated the roles of IL-2R alpha, IL-2R beta, and CD2/LFA-3 in the molecular regulation of NK cell granulocyte/macrophage-colony-stimulating factor (GM-CSF) production. Enriched populations of peripheral blood NK cells were separated into CD16-positive and CD16-negative fractions by flow cytometry; positively selected cells were greater than 97% positive for CD16 (the FcIII receptor for IgG which is present on almost all NK cells), less than 1% positive for the T cell antigen CD3, and did not demonstrate rearrangement of the T cell receptor beta chain gene by Southern blot. NK cell supernatants were harvested after 3-4 d of incubation with 0-100 U/ml IL-2, or after incubation with anti-CD2 (T11(3] MAb and sheep red blood cells (SRBC are a homologue for LFA-3). Parallel cell aliquots were harvested at 3-16 h for transcriptional run-on assays, S1 nuclease assays, and actinomycin D mRNA t1/2 determinations. IL-2-activated NK supernatants contained large amounts of GM-CSF (178 +/- 35 pg/ml) by ELISA as did supernatants from CD2-activated NK cells (T11(3) MAb + SRBC: 212 +/- 42) vs. less than 20 pg/ml for NK cells incubated alone or with either SRBC or T11(3) MAb alone. Sepharose-linked anti-CD3 MAb did not induce GM-CSF release from NK cells. By S1 analysis, both IL-2 and CD2 stimulation markedly augmented GM-CSF mRNA expression but with very different latencies of onset. IL-2R beta MAb inhibited greater than 85% of GM-CSF release from IL-2-activated NK cells and markedly suppressed IL-2-induced GM-CSF mRNA expression, whereas IL-2R alpha MAb even at 2,000-fold molar excess of IL-2 had little effect (less than 10%) on either GM-CSF release or mRNA expression. Run-on assays showed that GM-CSF is constitutively transcribed in NK cells and that IL-2 and CD2-activated cells had a three- to fourfold increased rate of GM-CSF transcription compared to nonstimulated cells. The t1/2 of GM-CSF mRNA in IL-2-activated NK cells was identical to that of unstimulated NK cells (15 min), whereas GM-CSF mRNA t1/2 in CD2-activated NK cells was increased 2.5-fold. We conclude that GM-CSF production in NK cells is regulated by both the IL-2Rbeta and the CD2 receptor but not by IL-2Ralpha, that both transcriptional and posttranscriptional signals act together to modulate the level of GM-CSF mRNA in NK cells, and that the molecular mechanisms underlying NK cell GM-CSF production are dependent in part on differential surface receptor activation.
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PMID:Production of granulocyte/macrophage-colony-stimulating factor by human natural killer cells. Modulation by the p75 subunit of the interleukin 2 receptor and by the CD2 receptor. 167 38

We measured soluble interleukin 2 receptor, a part of the Tac protein (p55), in peripheral blood to study the immunological condition of the T cell in autoimmune thyroid disease. In 26 patients with untreated Graves' disease and 7 hyperthyroid patients with Hashimoto's thyroiditis, the mean levels of soluble IL-2 receptor were both significantly higher than in normal controls (1497 +/- 649 (mean +/- SD), 641 +/- 137 vs 221 +/- 63 10(3) U/l, p less than 0.001). There was good correlation between soluble IL-2 receptor levels and blood thyroxine levels (r = 0.684, p less than 0.001) in patients with untreated Graves' disease, but no correlation of soluble IL-2 receptor with TSH-inhibitory immunoglobulins, TS-ab, thyroidal autoantibodies to thyroglobulin and thyroidal microsomal antigen was found. We thought that the level of soluble IL-2 receptor is not dependent only on immunological conditions, but also on thyroid hormone status. When T3 was administered to subjects in remission from Graves' disease and in normal controls, the soluble IL-2 receptor levels significantly increased. Moreover, the mean level of soluble IL-2 receptor in patients with toxic multinodular goitre was also significantly higher than in normal controls (411 +/- 148 vs 221 +/- 63 10(3)U/l, p less than 0.05). We conclude that the soluble IL-2 receptor levels are higher in sera of subjects with elevated levels of thyroid hormone.
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PMID:Increased soluble interleukin 2 receptor levels in autoimmune thyroid disease. 168 85

We and others have shown that several T cell responses induced by the mitogen phytohaemagglutinin (PHA), including T cell colony formation, IL-2 receptor (IL-2R) expression, and IL-2 production are impaired in patients with AIDS and lymphadenopathy syndrome (LAS). We investigated whether phorbol myristate acetate (PMA) could act in synergy with PHA (as it does in healthy subjects) to enhance in vitro T cell responses of patients at all stages of infection by HIV. In AIDS patients with opportunistic infections (AIDS/OI), PHA + IL-2 + PMA led to a total disappearance of T cell colonies in 10/11 patients, among whom six already displayed very low numbers of colonies induced by PHA + IL-2 (less than 50 colonies/5 x 10(4) cells). In contrast, T cell colony formation induced by PHA + IL-2 + PMA was maintained or increased, compared with that induced by PHA + IL-2, in five out of six AIDS patients with Kaposi's sarcoma (AIDS/KS), 10/14 LAS and six out of seven HIV-seropositive asymptomatic (HIV+/AS) homosexuals. In these three groups of patients, a low percentage of colony cells induced by PHA + IL-2 + PMA expressed CD3 and CD4 molecules, but 50-89% of cells were IL-2R (Tac) positive, as in healthy controls. Studies on T cell activation and IL-2 production were performed on a selected group of 12 HIV-infected patients for whom sufficient numbers of lymphocytes could be obtained. PMA induced CD4 down-modulation in controls and in HIV-infected patients. However, CD3 down-modulation and induction of the Tac chain of IL-2R by PMA were significantly impaired in patients, compared with controls, and these two parameters were correlated. Although PHA alone induced virtually normal levels of Tac antigen on patients' cells, Tac induction by PHA + PMA was significantly decreased in patients versus controls. Cells from five out of 10 patients tested failed to produce detectable amounts of IL-2 after PHA stimulation, whereas IL-2 production increased significantly in all patients tested (n = 9) after PHA + PMA, with a level of IL-2 activity significantly higher than in controls. No correlation was found in this group of patients between the effects of PMA + PHA on T cell colony formation, Tac expression, or IL-2 production, as compared with PHA alone. Taken together, our results indicate that in vitro T cell functional studies with PMA may be useful to evaluate better the defects of T cell activation in HIV-infected patients.
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PMID:Effect of phorbol myristate acetate on T cell colony formation, interleukin-2 (IL-2) receptor expression and IL-2 production by cells from patients at all stages of HIV infection. 169 61

Human T lymphocyte proliferative response induced via CD28 molecule is analyzed. An anti CD28 MoAb, CLB-CD28/1, induces the proliferation of human peripheral blood mononuclear cells in the absence of other stimuli, indicating that CD28 molecule can directly mediate a mitogenic signal in this system. The mitogenic activity of MoAb CLB-CD28/1 on PBMC does not require MoAb interaction with monocyte Fc receptors, since F(ab')2 fragments from the MoAb are mitogenic to the same extent as whole IgG. Nevertheless, the activity depends on the presence of accessory cells, since purified T lymphocytes require addition of irradiated monocytes and interleukin 2 to proliferate when incubated with MoAb CLB-CD28/1. On the other hand, MoAb CLB-CD28/1 induces response to IL-2 in thymocytes in the absence of accessory cells. Cooperation of MoAb CLB-CD28/1 with three other MoAbs, recognizing CD3, CD5 and HLA Class I antigens, respectively, induces Tac antigen expression and IL-2 responsiveness in purified T lymphocytes. This effect is obtained without cross-linking of the MoAb. It does not rely on a physical association between CD28 and CD3, CD5 or HLA Class I molecules, as demonstrated by co-modulation experiments. These data indicate that expression of IL-2 receptor on T lymphocytes can result from interaction of multiple activation pathways and that some of them, such as those mediated by CD5 and HLA Class I antigens, previously reported to serve as modulatory circuits, can instead act as essential elements in the onset of T lymphocyte proliferation.
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PMID:Mitogenic activity of anti-CD28 MoAb CLB-CD28/1 on peripheral blood mononuclear cells and its cooperation with other anti-T cells MoAb in the activation of purified T lymphocytes. 170 Oct 62

Interleukin 2 (IL-2) is a potent immunostimulant that causes the release of secondary cytokines and the production of lymphokine-activated killer cells. We investigated the cellular and cytokine responses to injection of recombinant human IL-2 into the human cerebrospinal fluid of 11 patients with metastatic tumors involving the spinal or cerebral leptomeninges. After initial intraventricular IL-2 administration (1.25 x 10(5) to 2 x 10(6) Cetus units/injection), cerebrospinal fluid samples were collected at intervals from 0 to 24 h. Enzyme-linked immunosorbent assay results indicated that IL-2 levels gradually decreased during the first 24 h, with an average t1/2 between 4 and 8 h. Induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and interleukin 2 receptor (p55) was also assessed by enzyme-linked immunosorbent assay. Tumor necrosis factor alpha and interleukin 6 levels peaked at 2 to 4 h and 4 to 6 h, with concentrations between 71 to 1,714 pg/ml and 942 to 10,500 pg/ml, respectively. Interleukin 1 beta, gamma-interferon, and soluble IL-2 receptor peaked later, during 6 to 12 h; the levels achieved were 234 pg/ml, 25 NIH units/ml, and 207 units/ml, respectively. All cytokine concentrations returned to near baseline between 12 and 24 h; however, the soluble IL-2 receptor levels remained elevated. Additional observations included a rapid influx of neutrophilic leukocytes, followed by a prolonged presence of lymphocytes. These data indicate a broad and complex potential of the immune response in the central nervous system, as well as further define the cytokine cascade in response to IL-2 alone.
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PMID:Cytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein). 173 71


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