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)

We evaluated the activation state of thymic lymphocytes in patients with myasthenia gravis (MG) by cytofluorographic analysis of CD25 expression and by testing their sensitivity to recombinant interleukin-2 (rIL-2) in the absence of any known previous stimulation. We detected no phenotypic signs of activation in fresh MG thymic lymphocyte suspensions, while functional signs of activation were reflected in a significantly higher sensitivity to rIL-2 in MG patients than in controls. The responses to rIL-2 were time- and dose-dependent, were inhibited by a blocking anti-IL-2 receptor antibody, and were associated with an increase in CD25+ T cells in both patients and controls. The T cells with functional signs of previous activation may represent autoreactive cells involved in the autoimmune process and confirm thymus gland hyperactivity in MG. These cells could result from primary autosensitization against the thymic acetylcholine receptor (AChR)-like molecule or from altered migration of peripheral activated cells into an abnormal thymic environment. Our results also provide a clue for understanding the effect of thymectomy in myasthenia gravis.
J Neuroimmunol 1989 Sep
PMID:Evidence of enhanced recombinant interleukin-2 sensitivity in thymic lymphocytes from patients with myasthenia gravis: possible role in autoimmune pathogenesis. 280 88

The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long-term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV-I-infected cell populations.
J Clin Invest 1987 Sep
PMID:Interleukin 1 gene expression in adult T cell leukemia. 288 87

Sera and cerebrospinal fluid (CSF) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were analyzed by Western blotting, and normal human leukocytes were transformed by co-cultivation with HAM patients' leukocytes. The sera and CSF from all HAM patients formed specific bands with HTLV-1 viral proteins, including p19, p24, p28, p32, p40 and p53. After 2-3 weeks of co-cultivation, scattered foci of cell aggregates were noted on macrophage sheets. Surface markers of the transformed cells were OKT3(+), OKT4(+), OKT8(-), IL-2 receptor(+) and EBNA(-). Chromosome analysis showed a normal karyotype. HTLV-1 viral genome was integrated into DNA isolated from transformed cell lines. Electron microscopy revealed type C virus particles in transformed T-cell lines. These results indicate that peripheral leukocytes from HAM patients can transform HTLV-1-negative leukocytes and HAM patients have the potential to acquire adult T-cell leukemia in the future.
Jpn J Cancer Res 1987 Sep
PMID:Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. 288 13

In the burn patient, the mechanisms leading to impaired T lymphocyte activity are unclear. The capacity for T cell proliferation and the expression of Tac antigen (IL-2 receptor) was assessed during the post-burn period in patients with injuries ranging from 5-68% total body surface area. T cell-dependent (polyclonal) immunoglobulin synthesis, mixed lymphocyte reaction and Interleukin-2 production were also determined in these patients and correlated with survival. Surviving patients demonstrated a transient reduction while terminal patients exhibited a permanent reduction in the number of Tac (+) lymphocytes, unrelated to the absolute number of T cells, during the post-burn period. The reduced percentage of IL-2 receptor-expressing T cells coincided with the suppressed antibody response and reduced alloreactivity. Although the concentration of IL-2 was decreased in all patients throughout the hospitalization period, surviving patients showed a gradual increase in its production while terminal patients gradually decreased to undetectable levels. Exogenous recombinant IL-2 induced a significant enhancement of in-vitro polyclonal immunoglobulin production and blastogenesis in the mixed lymphocyte reaction in immunosuppressed patients who demonstrated up to 50% reduction in the percentage of IL-2 receptor positive cells. Thus, the reduced capacity for production of and response to IL-2 after thermal injury may lead to the immunosuppression due to a lack of T lymphocyte clonal expansion. The permanent nature of this defect in patients who died from fatal sepsis may suggest a causative relationship.
Clin Exp Immunol 1986 Sep
PMID:Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression. 294 98

The role of interleukin 2 (IL-2) in the activation of suppressor T cells was investigated by using the monoclonal antibody anti-Tac, which blocks the binding of IL-2 to the 55-kDa peptide of the high-affinity IL-2 receptor. Anti-Tac was added to an antigen-nonspecific suppressor system in which Con A-induced suppressor T cells were generated during a preculture period, and their effects on immunoglobulin production were assessed in second, indicator cultures containing pokeweed mitogen and peripheral blood mononuclear cells. Anti-Tac added during the preculture period inhibited Con A-induced suppressor T-cell generation. Cells activated by a short (2-day) preculture period to become effectors of suppression were primarily of the Tac-positive, T8 (CD8)-positive phenotype. Tac-positive, T8-negative T cells might also contribute to the suppressor activity. Our studies indicate that anti-Tac, by producing a functional blockade of human high-affinity IL-2 receptors, inhibits the generation of antigen-nonspecific suppressor T cells.
Proc Natl Acad Sci U S A 1988 Sep
PMID:Blockade of the interleukin-2 receptor by anti-Tac antibody inhibits the generation of antigen-nonspecific suppressor T cells in vitro. 297 Jun 41

Our method of adoptive immunotherapy (AIT) using autologous IL-2-cultured lymphocytes differs from so-called LAK therapy in several points. We (1) obtain cultured lymphocytes from effusion lymphocytes (EL) or regional lymph-node lymphocytes (RLNL), when possible, rather than peripheral blood lymphocytes (PBL), (2) use crude IL-2 to induce T cell proliferation and to maintain killer activity, (3) use sonicated autologous tumor extract as antigen (Ag) to stimulate proliferation of cytotoxic T cells, and (4) pretreat the patients with local administration of OK-432 before AIT to induce effector cells that act synergistically with transferred killer cells. Surface marker analysis showed that OKT3, IL-2 receptor, Leu 2+15- cells were elevated while Leu 11a and Leu 3+8+ cells were decreased. Culture of RLNL augmented the expression of Leu 3+8- marker. Both of PBL and RLNL responded to Ag, and their auto-tumor killing activities were augmented in about half of the patients while rarely decrease by the addition of Ag. Response rates of patients with pleural effusion due to breast cancer and those with liver metastasis of breast cancer were 94% and 60%, respectively. Moreover, the survival was prolonged in the treated patients with pleural effusion or gastric cancer patients with peritoneal dissemination.
Hum Cell 1988 Sep
PMID:[Clinical therapeutic effect of adoptive immunotherapy using IL-2-cultured autologous lymphocytes]. 297 6

Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.
Cancer Res 1985 Sep
PMID:Interleukin 2 receptor (Tac antigen) expression in HTLV-I-associated adult T-cell leukemia. 299 Jun 87

Complementary DNAs corresponding to the human receptor for interleukin 2 (IL-2) have been molecularly cloned, sequenced, and expressed in COS-1 cells. The human genome appears to contain a single structural gene for this receptor; however, when transcribed at least two messenger RNAs (mRNAs) are produced which vary in length due to the use of different polyadenylation signals. Sequence analysis of the cloned complementary DNAs indicates an alternate pathway of mRNA processing for this receptor. Splicing of a 216 base pairs segment contained within the protein coding region results in an mRNA unable to code for the IL-2 receptor. In contact complementary DNAs corresponding to unspliced mRNA encode membrane receptors which bind both IL-2 and anti-Tac (monoclonal anti-IL-2 receptor antibody). Analysis of the deduced amino acid sequence reveals that the receptor is composed of 272 amino acids including a signal peptide 21 amino acids in length. Hydrophobicity analysis suggests a single 19 amino acid transmembrane domain. A short intracytoplasmic domain composed of 13 amino acids is present at the carboxy terminus and contains three potential phosphate acceptor sites (serine and threonine but not tyrosine) and typical positively charged amino acids presumably involved in cytoplasmic anchoring. Two sites for N-linked glycosylation sites and numerous extracytoplasmic O-linked glycosylation sites are present.
Cancer Res 1985 Sep
PMID:Isolation and expression of complementary DNAs encoding the human interleukin 2 receptor. 299 Jun 88

Interleukin 2 (IL-2) functions in the regulation of cell-mediated immune responses both in vivo and in vitro. Therefore, IL-2 production has been studied in patients with immunological disorders to determine the level of the immune defect. However, the cause(s) of low responses to selected antigens by cells from clinically normal individuals has not been examined. The ability of cells from clinically normal individual cattle to produce and respond to IL-2 was investigated as a measure of specific cell-mediated immune response. Cells from the majority of animals (6/7 in a representative experiment) could produce IL-2 in response to mitogen or a specific antigen, Bovine Herpesvirus 1 (BHV-1). Proliferation of lymphocytes from the majority of low responding animals (2/3 and 4/4 in separate experiments) could be restored to a level similar to high responders by the addition of exogenous IL-2 after endogenous IL-2 depletion. IL-2 receptor expression was indirectly assessed by the ability of activated cells to absorb IL-2. One individual's cells were incapable of absorbing exogenous IL-2 and failed to proliferate indicating a lack of activation and expression of receptors. In addition, exogenous IL-2 was able to enhance proliferation of both high and low responders in the presence of endogenous IL-2. These results suggest that proliferation of bovine peripheral blood mononuclear cells is dependent on the presence of IL-2. In addition, IL-2 production can be used to measure specific cell-mediated immune responses.
Vet Immunol Immunopathol 1986 Sep
PMID:Detection of impaired T cell-mediated immune responses to herpesvirus (BHV-1) in cattle. 302 Jul 71

Elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) inhibits interleukin 2 (IL-2)-stimulated proliferation of a murine cytotoxic cell clone, CT6. The effects of antiproliferative dosages of stable cAMP-derivative, 8-bromoadenosine 3':5'-monophosphate (8-Br-cAMP), on steady state mRNA expression stimulated by IL-2 was examined. IL-2 stimulated mRNA accumulation of three nuclear proto-oncogenes c-fos, c-myc, and c-myb. 8-Br-cAMP alone stimulated c-fos, c-myb, and IL-2 receptor mRNA accumulation as determined by Northern blot analysis. 8-Br-cAMP, however, markedly inhibited c-myc expression stimulated by IL-2. Furthermore, although c-fos and IL-2 receptor mRNA expression was potentiated by 8-Br-cAMP, suppression of protein synthesis was seen. We show that antiproliferative cAMP stimulates similar mRNA expression as does IL-2, with the exception of c-myc. Although a comparative stimulation of steady state mRNA accumulation of some genes occurs, cAMP may profoundly effect protein synthesis. cAMP, therefore, acts on multiple targets involved in the macromolecular events stimulated by IL-2.
J Immunol 1987 Sep 15
PMID:Effects of anti-proliferative cyclic AMP on interleukin 2-stimulated gene expression. 304 Aug 63


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