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)

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

Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognized the IL-2 receptor, has been used to purify the receptor. The recognized the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-Kd glycoprotein comprised of 272 amino acids including a single 19-amino transmembrane domain and a short intracytoplasmic domain composed of 13 amino acids at the carboxy terminus. Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-Kd long open reading frame (tat) protein encoded in part by the tat region of HTLV-I may act as a transacting activator that induces transcription of the IL-2 receptor gene, thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac-positive ATL are being treated with both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The interleukin-2 receptor on normal and malignant lymphocytes. 288 69

The gene encoding the human Interleukin 2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Receptor gene transcription is initiated at two principal sites in normal activated T cells. Adult T cell leukemia cells infected with HTLV-I show activity at both of these sites, but also at a third transcription initiation site. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hour after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hours after stimulation, reach peak levels between 8 and 24 hours, and then decline. Thus in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hours the peak and decline of IL-2 receptor protein expression occurring at the cell surface. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation.
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PMID:Structure and function of the human interleukin 2 receptor gene. 288 56

In HTLV-I transformed T-cell lines established from the patients with adult T-cell leukemia (ATL), there is a constitutive activation of the normal IL-2 receptor (IL-2-R) gene. These cell lines continuously produce an ATL-derived factor (ADF), an IL-2-R inducing factor without IL-2 activity. ADF enhances the expression of the IL-2-R through the augmentation of the IL-2-R mRNA in the HTLV-I(+) T-cell line (ED) as well as the NK cell line cells (YT). In YT cells, the transcriptional initiation of the promoter of the IL-2-R gene was enhanced by ADF but not by IL-2. Production of ADF by HTLV-I(+) T-cell lines may be involved in the abnormal expression of IL-2-Rs on these cells.
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PMID:Transcription of IL-2 receptor gene is stimulated by ATL-derived factor produced by HTLV-I(+) T cell lines. 288 66

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.
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PMID:Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. 288 13

Antigen-induced activation of resting T-cells induces the synthesis of interleukin-2 (IL-2), as well as the expression of specific cell surface receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. We have identified two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody, and a novel 75-kd non-Tac IL-2 binding peptide. Cell lines bearing either the p55, Tac, or the p75 peptide alone manifested low-affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high- and low-affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generates hybrid membranes bearing high-affinity receptors. We propose a multichain model for the high-affinity IL-2 receptor in which both the Tac and the p75 IL-2 binding peptides are associated in a receptor complex. In contrast to resting T-cells, human T-cell lymphotropic virus I-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T-cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are being treated with either unmodified or toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The role of the multichain IL-2 receptor complex in the control of normal and malignant T-cell proliferation. 289 1

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

Antigen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2), as well as the expression of specific cell surface receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. We have identified two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody and a 75-kd non-Tac IL-2 binding peptide. Cell lines bearing either the p55, Tac, or the p75 peptide alone manifested low-affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high- and low-affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. We propose a multichain model for the high-affinity IL-2 receptor in which both the p55 Tac and the p75 IL-2 binding peptides are associated in a receptor complex. The p75 peptide is the receptor for IL-2 on large granular lymphocytes and is sufficient for the IL-2 activation of these cells. In contrast to resting T cells, human T-cell lymphotropic virus I-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are being treated with either unmodified or toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor.
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PMID:The role of the multichain IL-2 receptor complex in the control of normal and malignant T-cell proliferation. 289 96

Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/- SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s-IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL-2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s-IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex-matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture.
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PMID:Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers. 290 Feb 31


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