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)

Studies of NF-kappa B suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-kappa B, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd polypeptide and its regulatory subunits I kappa B and p65. All four members of this kappa B-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR. These findings suggest a Rel-related family of kappa B enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is linked to its inhibitory action on cellular genes under NF-kappa B control.
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PMID:The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. 222 78

Anti-Tac(Fv)-PE40 is a recombinant single-chain immunotoxin containing the heavy and light variable regions of the anti-Tac monoclonal antibody fused to a mutant form of Pseudomonas exotoxin (PE). Anti-Tac binds to the p55 subunit of the human interleukin 2 (IL-2) receptor, and anti-Tac(Fv)-PE40 kills human or monkey cell lines that contain either the intact IL-2 receptor or its p55 subunit alone. To assess the usefulness of anti-Tac(Fv)-PE40 in treatment of IL-2 receptor-positive leukemia, we tested peripheral blood mononuclear cells from six patients with adult T-cell leukemia. In each of the six patients, anti-Tac(Fv)-PE40 was extremely cytotoxic to the malignant cells. Metabolic activity and sensitivity of the fresh cells improved when a small amount of IL-2 (10 units per ml) was present during incubation. The toxin concentration necessary to inhibit protein synthesis by 50% after 16-hr incubation of cells with immunotoxin varied from 1.6 to 16 ng/ml (2.5-25 x 10(-11) M). In every case, binding was by means of the Tac antigen because anti-Tac(Fv)-PE40 cytotoxicity was prevented by adding excess anti-Tac antibody. Moreover, anti-Tac alone or an inactive mutant of anti-Tac(Fv)-PE40 without ADP-ribosylation activity had very little cytotoxic activity. Peripheral blood mononuclear cells from normal controls, from a patient with Tac-negative leukemia, and from adult T-cell leukemia patients without significant peripheral blood involvement were not sensitive to anti-Tac(Fv)-PE40. These results indicate that anti-Tac(Fv)-PE40 is a potent cytotoxin against adult T-cell leukemia cells in vitro and warrants clinical testing.
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PMID:The recombinant immunotoxin anti-Tac(Fv)-Pseudomonas exotoxin 40 is cytotoxic toward peripheral blood malignant cells from patients with adult T-cell leukemia. 223 41

We investigated the inhibitory effects of purified recombinant hepatitis B virus (HBV) surface antigen (rHBsAg) and core antigen (rHBcAg) on lymphokine-activated killer cell (LAK) activity. Either peripheral blood mononuclear cells (PBMCs) or CD16+ CD3- LAK precursors, both of which were pre-incubated with interleukin-2 (IL-2) and rHBsAg or rHBcAg for 72 h, showed a significant decrease in LAK cytotoxicity against Daudi cells, in comparison to the results recorded in the presence of IL-2 alone, or IL-2 and E. coli extracts. This inhibitory effect was dose-dependent and was observed to be time-dependent from 24 to 72-h-cultures with these HBV antigens. This influence was not mediated with either adherent cells or other accessory cells. The proliferative reaction of either PBMCs or the LAK precursors after being cultured with IL-2 and rHBsAg or rHBcAg for 72 h was significantly diminished compared with the levels of reaction of those cells after a 72-h culture with IL-2 alone or with IL-2 and E. coli extracts. The levels of IL-2-driven IL-2 receptor (p55) expression of either PBMCs or the LAK precursors in the presence of rHBsAg or rHBcAg were higher than the levels seen in the absence of these HBV antigens. These results suggest that HBsAg and HBcAg may inhibit the induction of LAK activity by interfering with the proliferative reaction of the LAK precursors to IL-2 without inhibiting the IL-2 receptor expression of the cells. Cytofluorographic analysis of PBMCs, cultured with rIL-2, showed lower percentages of CD3+ and CD16+ cells in the presence of these HBV antigens than those in the absence of antigens.
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PMID:Inhibitory effects of hepatitis B virus antigen on induction of lymphokine-activated killer cell activity. 225 31

Bovine uterine luminal proteins (ULP) collected on Day 17 of pregnancy were tested for inhibition of binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) of bovine (CLC) and human (HLC) T lymphocytes and for binding to IL-2. Additional experiments assessed IL-2 binding to the p55 alpha chain (Tac protein) of the IL-2R of HLC. High- and low-molecular weight (Mr) ULP components (H-ULP greater than 248,000 Mr and L-ULP 21,000 Mr, respectively) inhibited (p less than 0.05 and 0.01, respectively) the binding of 125I-IL-2 to the IL-2R of CLC, whereas only H-ULP inhibited (p less than 0.05) binding to the IL-2R (presumably, the p75 beta chain) of HLC. H-ULP failed (p greater than 0.05) to bind to the p55 alpha chain of the IL-2R of HLC. For IL-2 binding, L-ULP failed (p greater than 0.05) to bind 125I-IL-2 in short (2 h)-term and long (45 h)-term experiments, whereas binding was evident (p less than 0.05) for H-ULP at 2 h of incubation. For H-ULP, mean (+/- SEM) percentages for bound and unbound 125I-IL-2 were 70.1 +/- 11.4 and 29.9 +/- 11.4, respectively. Further purification of H-ULP yielded a component (1.76 x 10(6) Mr) that bound 11.7% of 125I-IL-2 and inhibited (p less than 0.01) thymidine uptake and binding of 125I-IL-2 to the IL-2R of CLC. H-ULP-mediated suppression of lymphocyte proliferation may result from blocking IL-2R recognition of IL-2 as well as binding to IL-2, whereas suppression by L-ULP may predominantly result from blocking IL-2R.
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PMID:Interaction of bovine uterine luminal protein with interleukin-2 and the interleukin-2 receptor of T lymphocytes. 228 14

The lymphocytosis manifested in infectious mononucleosis (IM) during acute phase is ascribed to a reactive expansion of CD8+ T lymphocytes caused by Epstein-Barr virus (EBV)-infected B lymphocytes. Expression of HLA-DR antigen on IM lymphocytes suggests that these T lymphocytes are somehow activated in vivo. In the present study, we analyzed the interleukin-2 (IL-2) receptor expression on lymphocytes from six patients with acute IM. Radiolabeled IL-2 binding assay revealed that IM lymphocytes from all patients examined had a considerable number of IL-2 binding sites with an intermediate affinity, although they did not express the IL-2 receptor recognized by anti-Tac antibody (p55). The number of binding sites (1,070 to 4,600 sites per cell) was larger than that of a normal, resting T lymphocyte-enriched population (650 sites per cell). Furthermore, IM lymphocytes showed marked proliferative responses to higher concentrations of IL-2, which were almost completely blocked by an anti-p70 IL-2 receptor antibody, indicating that their IL-2 receptor is a functional receptor. The results of an affinity cross-linking study seem to indicate that the IL-2 receptor expressed on IM lymphocytes is p70, the second chain of the IL-2 receptor distinct from p55. Flow cytometric analysis following immunofluorescent staining with anti-p70 IL-2 receptor antibody confirmed p70 expression on CD8+ HLA-DR+ lymphocytes. These data suggest that p70 IL-2 receptor expression is involved in the immune response triggered by EBV infection.
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PMID:Selective expression of the p70 subunit of the interleukin-2 receptor on lymphocytes from patients with infectious mononucleosis. 229

The interleukin-2 diphtheria toxin-related fusion protein (IL-2 toxin) inhibits protein and DNA synthesis IN rIL-2 (10(-10) M) stimulated T lymphoblasts in a dose-dependent fashion. However, prior to target cell death very low concentrations of rIL-2 and IL-2 toxin synergistically stimulate [3H] thymidine incorporation despite inhibition of [14C] leucine uptake. A sequential analysis of [3H] thymidine incorporation shows that high IL-2 toxin concentration (10(-9)-10(-7) M) stimulates DNA synthesis at 18 hr of culture and inhibits [3H] thymidine uptake after 24 hr, while low concentrations of IL-2 toxin (10(-12)-10(-10) M) exhibits stimulatory effects only after 24 hr of culture. Anti-Tac a monoclonal antibody directed against the p55 chain of the high affinity IL-2 receptor (IL-2R) blocks the stimulatory effects of high-dose IL-2 toxin, thereby proving that these effects are mediated through the IL-2 domain of the fusion protein. At 7 hr following interaction with IL-2R receptor (IL-2R)+ T cells, IL-2 toxin-treated cells evidence augmented transcription of the heat shock protein gene, an effect indistinguishable from those mediated by rIL-2. We conclude that interaction of IL-2 toxin with IL-2R+ T cells initially mimicks the stimulatory effects of IL-2 upon gene transcription and DNA synthesis yet concomitant inhibition of protein synthesis is evident.
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PMID:A kinetic analysis of the effects of interleukin-2 diphtheria toxin fusion protein upon activated T cells. 230 Oct 12

Patients with chronic renal insufficiency under maintenance dialysis present numerous immunological alterations to which renal impairment, nutritional disturbances, blood transfusions and biocompatibility of the dialysis system may contribute. Although presently less frequent, infections still represent an important source of mortality and morbidity. Polynuclear neutrophils chemotactic responses are decreased and bactericidal capacity reduced, especially in polytransfused patients with iron overload. Lymphocyte counts are diminished and T lymphocytes present several alterations, including defective IL-2 synthesis, spontaneous expression of the p55 (CD25) chain of IL-2 receptor with high serum levels of this molecule, and defective T helper function in antibody production. Such alterations may account for the defect of delayed hypersensitivity reactions and the diminished antibody response after vaccination. Complement activation, increased expression of adhesion molecules by leukocytes, production of IL-1 and reduced oxygen molecular species during dialysis might contribute to immunological disorders of these patients.
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PMID:[Immune deficits in hemodialysis patients]. 232 86

Recombinant technology has facilitated the production of two soluble forms of human p55 interleukin-2 receptor (IL-2R) in Chinese hamster ovary cells. We have developed a ligand-affinity method for the medium-scale purification of these two soluble forms of the IL-2R, based on the biochemical interactions between the matrix-bound ligand (interleukin-2) and its soluble receptor. The affinity-purified IL-2R is further purified by anion-exchange chromatography followed by gel filtration. This method has provided enough highly pure IL-2R for structure and function studies and for use in practical applications such as high-flux drug-screening assays. The purified IL-2R subsequently has been immobilized on silica gel and employed for the purification of recombinant IL-2. Receptor-affinity-chromatography-purified IL-2 contains only a highly active monomeric form of the lymphokine, in contrast to immunoaffinity chromatography where several molecular forms of IL-2 with varying degrees of biologic activity are recovered. Receptor-affinity chromatography has been successfully applied to the purification of several mutant IL-2 as well as an IL-2-Pseudomonas exotoxin (IL2-PE40) fusion protein that is a 54.5-kDa chimeric protein in which the cell recognition domain is replaced by IL-2. The IL-2-PE40 is a potential cytotoxic agent for cells bearing the IL-2 receptor.
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PMID:Purification of the IL-2 receptor (TAC) by ligand-affinity chromatography and utilization of the immobilized receptor for receptor-affinity chromatography (RAC) purification of IL-2, mutant IL-2, and IL-2 fusion proteins. 235 48

IL-2 receptors on T cells exist in at least three forms which differ in their ligand-binding affinity. The low-affinity IL-2 receptor (IL-2R) consists of the 55-kDa Tac protein (p55 alpha), the intermediate-affinity site corresponds to the 70-kDa molecule (p70 beta), and the high-affinity IL-2R consists of a noncovalent heterodimeric structure involving both p55 alpha and p70 beta. We studied 24 B cell lines (8 EBV-negative and 16 EBV-positive) for IL-2R expression in the presence or absence of the tumor promoter, teleocidin. 125I-IL-2 radioreceptor binding assays and crosslinking studies demonstrated the sole expression of p55 alpha in EBV-negative cell lines only, whereas p55 alpha present in EBV-positive cell lines was always associated with p70 beta to construct high-affinity IL-2R. p70 beta was not detected in any of the EBV-negative cell lines, but was expressed on most of the EBV-positive cell lines (13 of 16). Our data also indicate that the expression of p55 alpha and p70 beta by radiolabeling correlates with their expression in flow cytometry, and that a large excess of p55 alpha is required to construct high-affinity IL-2R. Coexpression of p55 alpha and p70 beta on human B cells contributed to constructing high-affinity IL-2R hybrid complex as shown by (i) rapid association rate contributed by p55 alpha and slow dissociation rate by p70 beta; (ii) teleocidin's ability to induce p55 alpha on cell lines which express p70 beta only, resulting in appearance of high-affinity IL-2R; (iii) blocking p55 alpha by anti-Tac mAb in cell lines which constitutively express high-affinity IL-2R eliminated both high- and low-affinity components. The existence of low, intermediate, and high IL-2R on human B cells bears important future implications for understanding the mechanism of IL-2 signaling and the role of IL-2 in B cell activation, proliferation, and differentiation.
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PMID:Expression of low-, intermediate-, and high-affinity IL-2 receptors on B cell lines derived from patients with undifferentiated lymphoma of Burkitt's and non-Burkitt's types. 236 38

We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets were employed during incubation to facilitate interaction between T-cell LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55 expression after three to six days of culture with IL-2. Next we assessed the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2 blockade on IL-2-induced inhibition of BFU-E in autologous cocultures containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition (52% to 92%) of BFU-E in the presence but not in the absence of CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a 65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2) U/mL IL-2. Preincubation of CD3-triggered T cells with isotype control antibody had no effect on IL-2-induced erythroid inhibition. Day 3 supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T cells established in the presence of IL-2 were next assessed for modulation of BFU-E. CD3-triggered T-cell supernatants caused a 77% +/- 9% inhibition of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma) release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of culture. In control experiments, the addition of IF gamma-neutralizing monoclonal antibody to CD3-triggered T-cell supernatant established in the presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We conclude that blockade of the CD2 T-cell determinant induces down modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release. These data suggest that the T-cell CD2 determinant can exert a regulatory effect on the control of erythropoiesis by the lymphokine cascade.
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PMID:The T-cell CD2 determinant mediates inhibition of erythropoiesis by the lymphokine cascade. 245


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