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)

Human lymphotropic virus, HTLV-1, encodes in its proviral genome a transcriptional activator protein, tax-1, that may be responsible for the development of virus-induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin-2 (IL-2) and one of its receptor (IL-2R) components, the IL-2 receptor alpha-chain (IL-2R alpha). In the present study, an expression plasmid containing tax-1 cDNA under the control of HTLV-1 LTR was introduced into mouse and human CD4-positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL-2R alpha; (ii) the IL-2R alpha expression was not permanent, as the IL-2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL-2R alpha expression in the transformants is due to a cell-cycle-regulated expression and function of tax-1. Furthermore, a proportion of the induced IL-2R in EL-4 was in high-affinity form, suggesting the association of the IL-2R alpha and the IL-2R beta chain (p70-75) components.
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PMID:Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR-linked tax-1 gene. 279 77

We report a rare case of adult T cell leukemia/lymphoma (ATLL) in which cardiac invasion was clinically demonstrated and treated effectively. A 45-year-old female was admitted because of exertional dyspnea and cervical tumors. The leukocyte count was 19,100/microliters with 20% of flower cells. HTLV-I antibody was positive. She was diagnosed as ATLL and treated with VEPA. She got remission for a short duration which was followed by relapse. OPEC was started as salvage therapy. In the course, extensive pericardial effusion was found in chest X-P. Pericardial puncture demonstrated ATLL cells and high titer of free IL-2 receptor (57,400U/ml) in the effusion. It was diagnosed as pericardial invasion of ATLL cells. Chemotherapy was started with new combination of drugs (cisplatin, mitoxantrone, ifosfamide, and prednisolone). Concomitantly pericardial drainage was performed and the drugs were administered directly into the pericardial cavity. The clinical improvement was obtained and pericardial effusion did not appear thereafter. She died 4 months after the diagnosis of cardiac invasion. On autopsy myocardial invasion was identified. The pericardium widely adhered and effusion measured 42 ml.
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PMID:[Cardiac invasion of ATLL cells and therapeutic effects of local along with systemic treatments]. 281 Jul 92

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL-2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.
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PMID:Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement. 286 23

Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL-2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A-stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation.
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PMID:IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. 287 15

Cocultivation of spleen cells, lymph node cells, and thymocytes of female Wistar-King-Aptekman rats with short-term cultured male adult T cell leukemia (ATL) cells in the presence of 5-bromo-2'-deoxyuridine (BudR) resulted in the establishment of rat lymphoid cell lines, TARS-1, TARL-2, and TART-1. Cytogenic analysis of the three cell lines showed a female rat karyotype with 42 chromosomes. The surface phenotypes of TARS-1 and TART-1 were those of rat T cells. TARL-2 was only positive for rat Ia and leukocyte common antigens and brain associated T antigen. The cell lines continuously produced a type C retrovirus, human T cell leukemia virus-I (HTLV-I) and expressed ATL-associated antigens. By using monoclonal antibodies for rat IL-2 receptors, FACS analysis demonstrated that three rat T cell lines unequivocally expressed rat IL-2 receptor. TARS-1 and TART-1 but not TARL-2 were transplantable into newborn syngeneic rats and nude mice. By injecting MMC-treated TARS-1 into newborn syngeneic rats, HTLV-I carrier rats were obtained which showed gradual increase of anti-ATLA antibody titer by aging. No evidence of leukemia nor malignant lymphoma were observed in those carrier rats. Adult rats immunized with these rat cell lines produced antibodies specific for HTLV-I. The biochemical analysis of the antigen that reacted with rat sera revealed that they are the HTLV-I specific polypeptides, p28, p24, p19 and p15.
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PMID:[Rat lymphoid cell lines producing human T cell leukemia virus-I]. 288 Jul 89

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.
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PMID:Interleukin 1 gene expression in adult T cell leukemia. 288 87

Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients.
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PMID:Close association between interleukin 2 receptor mRNA expression and human T cell leukemia/lymphoma virus type I viral RNA expression in short-term cultured leukemic cells from adult T cell leukemia patients. 289 29

In the present study, we examined the expression of interleukin 2 (IL-2) receptors on normal human B cells as well as established B cell lines. Anti-Tac monoclonal antibody did not bind to freshly separated normal human B cells. Unexpectedly, with the appropriate activation of the normal B cells by anti-mu antibody, phorbol myristate acetate, or Staphylococcus aureus Cowan I (SAC), Tac antigen was induced on the activated B cells. Anti-Tac antibody showed consistent reactivity with two B cell lines that were infected by human T cell leukemia virus (HTLV) and some reactivity with two out of eight Epstein-Barr virus-transformed B cell lines established from normal adult donors. Immunoprecipitation analysis revealed that antigens of similar size with a molecular weight of 50,000-60,000 can be precipitated with anti-Tac antibody from phytohemagglutinin-stimulated normal T cell blasts and normal activated B cells, as well as a cloned B cell line. Binding assays of IL-2 on normal activated B cells and on the cloned B cell (HS1) revealed that B cells have significantly fewer sites and lower-affinity IL-2 receptors compared with phytohemagglutinin-stimulated normal T cell blasts. Finally, biological properties of the IL-2 receptor on B cells were examined by incubating B cells with recombinant IL-2. It was found that moderate concentrations of IL-2 induce significant enhancement of proliferation and differentiation in SAC-activated normal B cells. These results suggest that normal B cells may express functional IL-2 receptors or closely related proteins and thus IL-2 may play a significant role in the modulation of B cell function.
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PMID:Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function. 298 52

Three rat lymphoid cell lines (TARS-1, TARL-2, and TART-1) (12) transformed by human T cell leukemia/lymphoma virus I (HTLV-I) had rearrangement of the beta chain gene of the T cell antigen receptor, and had integrated proviral DNA from HTLV-I in their genomes. As is the case with adult T cell leukemia (ATL)-derived human T cell lines transformed by HTLV-I, these rat cell lines unequivocally expressed interleukin 2 (IL-2) receptor, as determined by radiolabeled IL-2 binding. By Scatchard plot analysis, one of the cell lines, TART-1, proved to have high affinity receptors (Ka = 1.3 X 10(11)/M and 8.8 X 10(9)/M). Rat IL-2 receptor, not human IL-2 receptor, was expressed on HTLV+ rat cell lines, as demonstrated by the fact that they expressed antigens reactive with monoclonal antibodies (ART-18) against rat IL-2 receptor, but not with anti-Tac antibodies. The collective evidence indicates that the endogenous IL-2 receptor gene is activated in human and rat lymphoid cell lines with HTLV-I production. The mechanism of abnormal IL-2 receptor expression in HTLV infection is discussed.
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PMID:Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor. 298 31

Adult T cell leukemia (ATL) is an almost uniformly fatal malignancy of mature T cells associated with human T cell leukemia/lymphoma virus type 1 (HTLV-1) infection. Cells from this leukemia are characterized by the expression of large numbers of receptors for interleukin 2 (IL-2). In an attempt to prepare an immunotoxin with selective cytotoxicity for ATL cells, we conjugated anti-Tac, a monoclonal anti-IL-2 receptor antibody, to purified ricin A chains. Although unmodified anti-Tac had no effect on the protein synthesis of these cells, anti-Tac-ricin A chain conjugates produced half-maximal inhibition of protein synthesis in HTLV-1-infected leukemic T cell lines at concentrations of 2 to 6 X 10(-10) mol/L (ID50). An essentially identical ID50 was obtained with leukemic peripheral blood T lymphocytes isolated from two patients with ATL. In contrast, half-maximal inhibition of protein synthesis in HTLV-uninfected, IL-2 receptor-negative T and B cell lines required 200- to 1,000-fold higher concentrations of anti-Tac-ricin A chain conjugates. Both unconjugated anti-Tac and immunoaffinity-purified IL-2 completely inhibited the toxic effects of anti-Tac-ricin A, confirming the specificity of the conjugate-IL-2 receptor interaction. Clonogenic assays demonstrated that anti-Tac-ricin A chain was able to eliminate greater than 99.9% of an HTLV-1-infected T cell population at concentrations only marginally affecting IL-2 receptor-negative cells. The data presented demonstrate that anti-Tac-ricin A is selectively cytotoxic for HTLV-1-infected leukemic T cells in vitro and raises the future possibility of specific therapeutic intervention with immunotoxins in this disease.
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PMID:Adult T cell leukemia: a potential target for ricin A chain immunotoxins. 298 44


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