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)

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
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PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

Twenty-three monoclonal antibodies (MAbs) against the IL-2 receptor alpha-chain (CD25) were evaluated as ricin A-chain immunotoxins for the treatment of Hodgkin's disease. Primary screening used an indirect assay in which the cells were treated with the test antibody followed by a Fab' immunotoxin against mouse immunoglobulin. This screening identified 5 MAbs which inhibited protein synthesis in L540 Hodgkin cells by 50% at a concentration (IC50) of 6 x 10(-11) M or less: RFT5 gamma 1, RFT5 gamma 2a, B-B10, B-F2 and B-G3. These MAbs were then linked directly to deglycosylated ricin A-chain (dgA) and were confirmed to have potent and specific toxicity for L540 cells. The immunotoxins had the following potency order: RFT5 gamma 1 greater than RFT5 gamma 2a greater than B-B10 greater than B-F2 greater than B-G3. The most effective immunotoxin, RFT5 gamma 1.dgA, had an IC50 value of 7 x 10(-12) M, which is the same as that of whole ricin. In vivo, a single intravenous injection of 48 micrograms of RFT5 gamma 1.dgA, RFT5 gamma 2a.dgA, B-B10.dgA or B-F2 induced lasting complete remissions in 78, 66, 50 and 44%, respectively, of nude mice bearing subcutaneous solid L540 tumours of 0.7 cm diameter. Two tumours which regrew after B-B10.dgA treatment were re-established in tissue culture. Both had reduced sensitivity to B-B10.dgA in vitro but not to immunotoxins recognizing different antigens on Hodgkin cells. The MAbs that produced the most potent immunotoxins, RFT5 gamma 1, RFT5 gamma 2a and B-B10, had no significant cross-reactivity with normal human tissues outside the lymphoid system as judged from indirect immunoperoxidase staining of frozen sections. By contrast, B-F2 strongly stained normal human renal tubules.
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PMID:Immunotoxins constructed with anti-CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent anti-tumour effects against human Hodgkin cells in vitro and solid Hodgkin tumours in mice. 191 43

Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.
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PMID:Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes. 193 92

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.
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PMID:Immunologic markers in non-Hodgkin's lymphoma. 193 59

Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and soluble IL-2 receptor (sIL-2R) serum levels were evaluated in 24 hairy cell leukemia (HCL) patients. Of these, three patients were studied at the time of diagnosis, 12 in relapse after interferon (IFN) therapy, eight with a partial response after IFN and one with a complete response after 2-deoxycoformycin (DCF) therapy. Statistically significant differences were observed in the serum levels of IL-1 beta and sIL-2R between HCL patients and controls. These were 400.3 pg per 0.1 ml (range 23.2-990) and 64.3 pg per 0.1 ml (20-115) for IL-1 beta and 4667.2 U/ml (488-7800) and 424.3 U/ml (188-666) for sIL-2R, respectively. In contrast, IL-1 alpha measurements showed no statistical differences between the two groups. A significant increase of sIL-2R (p = 0.01) and IL-1 beta (p = 0.03) serum levels was observed in patients studied at the time of diagnosis or in relapse compared to those in partial or complete remission. IL-1 beta serum levels directly correlated with sIL-2R (p less than 0.0001) and with hairy cell (HC) bone marrow infiltration, expressed by the HC index (p = 0.003). The comparison of IL-1 beta serum levels of HCL patients with those detected among 149 patients grouped according to diagnosis (Hodgkin's disease = 17, non-Hodgkin's lymphomas = 57, acute non-lymphoid leukemia = 46, and acute lymphoid leukemia = 29) indicate that HCL patients showed the highest IL-1 beta serum level increase, indicating that IL-1 beta could be used as a specific clinical marker of this disease.
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PMID:Serum interleukin-1 beta levels correlate with neoplastic bulk in hairy cell leukemia. 207 45

Hodgkin and Sternberg Reed (H and SR) cells, the putative malignant cells of Hodgkin's disease carry regularly T-cell activation antigens, like CD30 and CD25 (low affinity IL-2 receptor). We have investigated the Hodgkin cell line L540, bearing characteristic markers of H and SR cells for its expression of the low affinity IL-2 receptor (IL-2R) and for IL-2. Expression of the low affinity IL-2R was found on mRNA level, by detection of specific 3.5 kb and 1.4 kb mRNA and on the protein level by immunoprecipitation of a 55,000 mol. wt molecule from detergent extracts of surface iodinated cells, however IL-2 specific mRNA was not detected. Scatchard plot analysis revealed the presence of 2 x 10(3) high affinity IL-2Rs. Crosslinking experiments directly demonstrated the high affinity IL-2R to consist of the 55,000 mol.wt light chain (L), and the 70/75,000 (H1/H2) heavy chains. IL-2 was rapidly internalized by these receptors, suggesting that they can be functional. The expression of functional IL-2Rs might be involved in induction or differentiation of Hodgkin's disease.
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PMID:High affinity IL-2 receptors on a Hodgkin's derived cell line. 228 Jun 10

Expression of the IL-2 receptor (Tac antigen/CD25) is documented in malignant lymphomas. Because IL-2 is a major lymphocyte growth factor, an IL-2-dependent growth could be involved in the proliferation of Tac-positive lymphomas. Indeed such a mechanism has been demonstrated experimentally for the growth of T-cell lines. To investigate this point in human lymphomas, we used in situ hybridization to analyze the expression of the IL-2 gene in 20 non-Hodgkin's lymphomas, among which 12 expressed the IL-2 receptor. Nine of these were anaplastic large cell lymphomas expressing the Ki-1-related antigen. We here show that IL-2-producing cells are present in all the lymphomas we analyzed. As a mean, there is no significant difference in the percentage of IL-2-producing cells between Tac-positive and -negative lymphomas. However, the level of IL-2 production is highly heterogeneous in both groups, and the highest density of IL-2-producing cells was observed in 2 Tac-positive lymphomas. Simultaneous detection of cellular antigens and of IL-2 mRNA demonstrates that IL-2 is produced by reactive T cells rather than by tumor cells. These results suggest that if IL-2 is involved in the growth of Tac-positive lymphomas, it acts as a paracrine, rather than an autocrine, factor.
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PMID:IL-2 mRNA expression in Tac-positive malignant lymphomas. 230 33

Interleukin 2 and its receptor have emerged as a central control system in the regulation of the immune response and the proliferation of T cells, B cells, and macrophage. IL-2 receptor expression is strongly associated with several forms of human lymphoproliferative disease including adult T-cell leukemia-lymphoma, hairy cell leukemia, Hodgkin's disease, and peripheral T-cell lymphoma in which it may play a pathogenetic role. IL-2 receptor expression may also play a role in some B-cell non-Hodgkin's lymphomas and histiocytic proliferations. Recent discoveries in immunology and advances in biotechnology have opened therapeutic possibilities for IL-2 including the use of anti-Tac monoclonal antibodies and immunoconjugates for the therapy of Tac-positive lymphoproliferative disease, the use of anti-Tac monoclonal antibodies as novel immunosuppressants, and the use of genetically engineered recombinant IL-2 and activated autologous lymphocytes in the adoptive immunotherapy of cancer. Therapeutic and diagnostic applications of IL-2 continue to be defined.
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PMID:Interleukin receptors in lymphoid lesions. Relevance to diagnosis, biology, and therapy. 267 80

The role of interleukin 2 (IL-2) for growth and differentiation of normal and malignant B cells still remains controversial. We assessed normal peripheral blood B cells and cell lines derived from patients with B non-Hodgkin's lymphomas (NHLs) with respect to their responsiveness to recombinant human IL-2 (rIL-2). The NHL cell lines used in our experiments expressed the Tac antigen (CD25)--a compound of the IL-2 receptor (IL-2R)--in a percentage ranging from 28 to 57%. As measured in a [3H]thymidine uptake assay, the normal peripheral blood B cells demonstrated a dose-dependent proliferative response to rIL-2, whereas the NHL cells did not show any responsiveness to rIL-2. In a clonogenic culture assay we evaluated the colony formation of the NHL cells and found a decrease of 28 to 41% on average in the presence of rIL-2 (10-50 U/ml). This moderate inhibitory effect on the clonal growth of the NHL cells was not due to a differentiation inducing effect of rIL-2, as studied by measuring the Ig production under increasing doses of rIL-2 (1 to 100 U/ml). Thus, malignant NHL B cells may express the CD25 compound of the IL-2 receptor on their surface, demonstrating a different functional responsiveness to rIL-2 compared to normal peripheral blood B cells.
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PMID:Effect of recombinant human interleukin 2 (rIL-2) on normal peripheral blood B cells and B lymphoblastoid cell lines. 268 Sep 16

One of 4 siblings affected by hereditary spinocerebellar ataxia (HSCA) of Marie's type developed Hodgkin's disease (HD): the stage was IV B, the patient was submitted to conventional chemo- and radiotherapy and achieved complete remission. An accurate clinical, genetic and immunological study was carried out on all his family, including a complete HLA typing, a chromosome study, the immunophenotyping of peripheral blood mononuclear cells (PBMC), the PBMC response to polyclonal mitogens, to interleukin 2 (IL-2), to the association of PHA + IL-2 and the evaluation of the IL-2 receptor expression. No association was clearly demonstrable between an HLA haplotype and HSCA, while the patient with HSCA and HD was HLA-B18- and DQw3-positive (the last at homozygous level), two antigens known to be strongly associated with HD, mainly among the Sardinian ethnic group. The mode of inheritance of HD susceptibility is however completely different from that of Marie's HSCA. The chromosome study did not show any characteristic pattern of the karyotype, neither of the HSCA affected nor of the unaffected members. The immunological investigations did not elucidate any characteristic behavior of the family members, apart from the typical findings of HD seen on patients with HSCA and HD. Our study could not demonstrate any genetic and/or immunologic common background shared by the two diseases, HSCA and HD. Their coexistence in our patient, although the statistic probability is very low, seems to be a fortuitous coincidence more than the result of a common genetic and pathogenetic mechanism.
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PMID:Hodgkin's disease presenting in 1 of 4 siblings affected by hereditary spinocerebellar ataxia: clinical, immunological and genetic study. 278 67


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