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)

A monoclonal antibody is described which recognises an epitope associated with a receptor for interleukin-2 (IL-2) on pig lymphocytes. The monoclonal antibody inhibits high affinity binding of radiolabelled recombinant human IL-2 (rhIL-2) by pig lymphoblasts and also non-competitively inhibits both pig-TCGF and rhIL-2 maintained proliferation. By flow cytometry the antigen is apparently not present on freshly isolated blood lymphocytes but is detectable on small cells between 6 and 12 h after activation and on large cells by 24-h. These findings are comparable with those obtained using monoclonal antibodies recognising the 55 kDa alpha chain of the human and mouse IL-2 receptor (p55, TAC) expressed on activated cells in vivo and in vitro. However, the molecular weight of the porcine antigen is between 65 and 70 kDa.
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PMID:A monoclonal antibody recognising an epitope associated with pig interleukin-2 receptors. 138 6

Interleukin 2 (IL-2) induced activation of unstimulated resting natural killer (NK) cells or resting T-cells initially occurs following binding of IL-2 through the p75 receptor that is expressed primarily by these cells. However, this IL-2/p75 interaction induces TAC chain synthesis and formation of high affinity IL-2 receptor required for the proliferation of resting peripheral blood lymphocytes. In this study, we present data indicating that NK cells activated by in vivo IL-2 treatment, in contrast to resting NK cells, respond and proliferate to further IL-2 in vitro using primarily the p75 receptor with only a minor component of cells responding through the high affinity receptor. These in vivo activated NK cells minimally expressed the TAC chain and maintained this TAC negative phenotype while proliferating in response to IL-2. The primary involvement of the p75 receptor in the proliferative response of these cells to IL-2 was demonstrated by the need for concentrations of IL-2 higher than 44 pM to obtain a significant response and by the dramatic inhibition of this response by anti-p75 monoclonal antibody. Anti-TAC monoclonal antibody inhibited only the poor proliferation obtained at low doses of IL-2 suggesting a minor role for TAC and high affinity IL-2 receptors. This was in contrast to the partial inhibition of proliferation by anti-p75 or anti-TAC observed in unstimulated pretherapy peripheral blood lymphocytes suggesting that these cells respond to IL-2 through both high affinity receptors and intermediate affinity p75 receptors. The T-cells isolated from in vivo activated peripheral blood lymphocytes, despite expressing TAC, were not responsive to IL-2, suggesting that these cells express predominantly nonfunctional low affinity TAC receptors. NK cells activated by IL-2 in vivo represent a unique model system of IL-2 dependent cells that respond and proliferate to IL-2 essentially through the p75 IL-2 receptor.
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PMID:Natural killer cells activated by interleukin 2 treatment in vivo respond to interleukin 2 primarily through the p75 receptor and maintain the p55 (TAC) negative phenotype. 169 79

Using a high-sensitivity immunofluorescence procedure, a proportion of blood lymphocytes can be shown to express the p55 chain of the IL-2 receptor (CD25, TAC) without in vitro stimulation. In this study, we measured the proportion of peripheral blood lymphocytes expressing CD25 in patients with a diagnosis of HIV infection and compared the results with cells from controls. The mean value for HIV-positive samples was 15%, while controls gave a mean value of 31%. The difference between the groups was highly significant (P less than 0.001, Mann-Whitney U test). When expression of CD25 was examined separately in CD4-positive and CD8-positive T cells and in B cells, there was a wider spread of values in the HIV group compared with controls, but no systematic difference. In the patient group studied (110 samples from 53 patients) there was a weak correlation between CD25 and CD4 expression (correlation coefficient r = 0.21, P less than 0.02), but there were patients with low CD25 and high CD4 as well as patients with high CD25 and low CD4, suggesting that CD25 can vary independently of changes in CD4 lymphocytes. Although the majority of very low values of CD25 (less than 10%) were found in patients with stage IV disease, such low values were also common in Stage II disease.
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PMID:Patients with HIV infection have a reduced proportion of lymphocytes expressing the IL2 receptor p55 chain (TAC, CD25). 170 15

Newborns are more susceptible to fungal, viral, protozoan, and certain bacterial infections than adults. This susceptibility is due in part to a decreased interferon gamma (IF gamma) production. The present investigation focuses on the role of the IL-2 receptor in the deficient IF gamma production in neonatal T cells. IL-2-induced IF gamma production in unstimulated neonatal cord blood and adult peripheral T cells was comparable, but the IF gamma production in CD3-stimulated neonatal T cells was only 20% of the adult production. Neonatal and adult T cells showed no difference in the expression of the 55-kD alpha and 75-kD beta chains of the IL-2 receptor. Blocking of the 55-kD alpha chain of the IL2 receptor with TAC MAb resulted in a marginal reduction in IF gamma release from unstimulated or CD3-stimulated neonatal T cells cultured in the presence of IL-2. In contrast, blocking of the 55-kD alpha chain of the IL-2 receptor in adult T cells caused a 92% and 73% inhibition in IF gamma production in unstimulated and stimulated T cells, respectively. Blocking of the 75-kD beta chain of the IL-2 receptor with TU27 MAb had a marginal effect in both unstimulated and CD3-stimulated neonatal and adult lymphocytes. Binding studies with unstimulated cord blood T cells using [125I]-IL-2 showed a binding affinity that corresponded with the intermediate affinity IL-2 receptor. In CD3-stimulated cord blood T cells, a high-affinity receptor was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective interferon gamma production in neonatal T cells is independent of interleukin-2 receptor binding. 183 81

The effect of interleukin-2 (IL-2) on IL-4-induced IgE and IgG4 secretion by B cells in peripheral blood mononuclear cell (PBMC) preparations from non-atopic healthy humans and atopic dermatitis patients was investigated. PBMC were cultured at an optimal concentration of recombinant IL-4 with or without addition of IL-2 for 10 days. Native and recombinant IL-2 inhibited the IL-4-induced IgE and IgG4 secretion in a dose-dependent manner by cells from both normal and atopic donors. Rabbit antibodies to IL-2 or to the monoclonal anti-IL-2 receptor antibody anti-TAC reversed the IL-2 effect. Culturing cells with IL-4 and IL-2 for 1 or 2 days only slightly suppressed the IgE and IgG4 secretion whereas addition of IL-2 to IL-4 containing cultures on day 4 or 5 inhibited the IgE and IgG4 secretion more effectively. This is in contrast to interferon-gamma (IFN-gamma) which inhibited the IL-4 induced IgE and IgG4 secretion when added for the first 24 or 48 h but had no effect when added on days 4 or 5. The data demonstrate that both IL-2 and IFN-gamma act as antagonists in the IL-4-induced IgE and IgG4 secretion by human B cells; while IL-2 appears to inhibit relatively late in culture, IFN-gamma has an early inhibitory effect, suggesting that the two lymphokines inhibit the IL-4 effect by different mechanisms.
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PMID:Interleukin-2 inhibits the interleukin-4-induced human IgE and IgG4 secretion in vivo. 190 25

The peripheral blood B-lymphocyte responsiveness to interleukin-2 (IL-2) has been studied in healthy donors. Unstimulated B-cells proliferated moderately in response to IL-2, this being not associated with an increase of TAC-positive cells. Phytolacca mitogen did not stimulate purified B-cells to proliferation and did not influence TAC expression and responsiveness to IL-2. S. aureus mitogen (SAC) provided a maximum proliferation in response to IL-2 with a dramatic increase of TAC expression. Simultaneous estimation of unstimulated and SAC-preactivated B-lymphocyte responses to IL-2, together with scintillation of TAC-positive cells, helps determine the degree of a possible injury to IL-2 receptor.
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PMID:[A system of assessing interleukin-2-dependent activation of B-lymphocytes]. 247 6

In this study, we describe a new methodology to detect and quantify lymphokine receptors, using interleukin-2 as a prototype. Human recombinant interleukin-2 (IL-2) was conjugated to fluorescein isothiocyanate. Binding of fluoresceinated IL-2 to different cell types was assessed by flow cytometry analysis, on a FACS 440 calibrated using fluoresceinated Sephadex G-25 beads. This calibration procedure allowed us to quantify the actual number of binding sites for IL-2. Fluoresceinated IL-2 did not bind to normal resting T cells, whereas a highly significant binding was observed on PHA-activated human T cells. The binding was inhibited by an excess of unlabeled IL-2 and by an excess of anti-IL-2 receptor p55 antibodies (anti-TAC). Dose curves of IL-2 showed a two plateau saturation, the first plateau corresponding to the saturation of high affinity binding sites, as assessed by correlation with the biological activity on IL-2-dependent T cells. Among the cell types tested, fluoresceinated IL-2 bound to IL-2-dependent mouse T cells (the binding in that case was not inhibited by anti-IL-2 receptor p55 antibodies), and to different p70 expressing cell lines or normal cells (MLA 144, normal large granular lymphocytes). Taken together, these results indicate that fluoresceinated IL-2 can be used to detect high as well as low affinity IL-2 binding sites.
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PMID:Detection of low and high affinity binding sites with fluoresceinated human recombinant interleukin-2. 249 69

Expression of the low-affinity interleukin-2 (IL-2) receptor molecule (TAC) has been associated with lymphocyte activation, in vitro and in vivo [Greene WC (1987) Clin Res 35:439]. We have used an enzyme-linked immunosorbent assay (ELISA) to quantify the role of released and cell-bound IL-2 receptor following in vitro or in vivo activation of human lymphocytes with IL-2. In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells. In 12 patients receiving high-dose IL-2 for the treatment of various malignant neoplasms, the levels of IL-2 receptor released into the serum rose dramatically during the IL-2 infusion, and then fell following cessation of the IL-2 infusion. This heightened release of IL-2 receptor into the serum occurred during the episodes of profound lymphopenia that developed within hours after patients began an IL-2 infusion. Following each 4-day infusion of IL-2, a rebound lymphocytosis was observed, as has been previously reported. Serum IL-2 receptor levels do not rebound in parallel; rather, they reach a plateau near the end of the 4-day infusion and then decrease upon cessation of IL-2. These changes in serum IL-2 receptor levels accompany changes in lytic activity of circulating PBL on Daudi target cells. These results suggest that lymphocyte populations exposed to IL-2 in vivo are activated to become cytotoxic, release TAC, and relocate in non-peripheral blood compartments. Following cessation of the IL-2 infusion these activated lymphocytes return to the peripheral circulation and do not secrete TAC as vigorously as while influenced directly by the IL-2 infusion.
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PMID:Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation. 278 94

Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of beta-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the beta-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of beta-adrenergic agonists on expression of the high affinity IL-2 receptors, [125I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of beta-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that beta-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites.
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PMID:Beta-adrenergic-receptor-mediated suppression of interleukin 2 receptors in human lymphocytes. 289 Jun 87

A human model of oral immunization using two forms of HI antigen preparation was studied. Oral immunization with killed HI (monobacterial) or HI in a polybacterial mix (polybacterial) induced an enhanced antigen-driven proliferative response in circulating PBL of normal subjects as well as an increase in the precursor frequency of HI antigen-specific cells using limiting dilution analysis. However, the proliferative response was better maintained at a high level in subjects after completion of immunization with the polybacterial vaccine, whereas the response was small and transient following oral immunization with the monobacterial vaccine. Clonal analysis of the proliferative response demonstrated that the precursor frequency of HI antigen-specific cells in the circulating pool was not expanded to account for the differences, despite repeated ingestion of the vaccine. An analysis of PBL following oral immunization using anti-TAC monoclonal antibody revealed an increase in the number of IL-2 receptor-bearing cells in subjects orally immunized with the polybacterial vaccine, with maximal numbers occurring at day 62 when the number of precursors fell but the proliferative response remained high. This suggests that the enhanced and sustained proliferation in bulk cultures is due in part to a contribution to the overall proliferation by in vivo polyclonally-activated IL-2 receptor positive cells which proliferate in the presence of IL-2. Taken together, the results obtained are consistent with the concept that 'restricted' cell activation may be important in the mechanism of selective protection found following oral immunization with monobacterial HI vaccine.
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PMID:Induction of antigen-reactive and IL-2 receptor bearing cells following oral immunization in humans. 312 36


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