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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to explain the molecular basis for the diverse pathology and clinical behavior of postthymic T cell malignancies. Total cellular RNAs were extracted from four HTLV-1 positive and ten HTLV-1-negative T cell lymphomas and cell lines, and investigated for homology with cloned DNA probes specific for interleukin-2 (IL-2), IL-2 receptor (IL-2R), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and epidermal growth factor receptor (EGF-R). Tumor cells associated with clinically high grade HTLV-1-positive adult T cell leukemia (ATL) and large cell morphology (T immunoblastic lymphomas) were found to have higher levels of expression of IL-2 and TGF-beta genes than low grade T cell neoplasms (mycosis fungoides and Sezary's syndrome). High expression of IL-2R gene was restricted to Ki-1-positive lymphomas and to one ATL. Cell lines corresponding to the advanced stage of a cutaneous T cell lymphoma (CTCL) showed enhanced expression of PDGF. Therefore, high grade T cell malignancies had consistently elevated expression of growth factor/receptor (GF/R) genes. Expression of EGF-R was negligible in all T cell malignancies. An inverse relationship was found between the expression of T cell antigen receptor (differentiation antigen) and GF/R (activation antigen) genes, accounting for the frequent aberrant expression of T cell antigens in high grade T cell lymphomas. The results suggest that post-thymic T cell malignancies derived from activated T cells produce and secrete GF, conferring a growth advantage on neoplastic T cells, and correlating well with their histologic subtype and clinical behavior.
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PMID:Expression of growth factor/receptor genes in postthymic T cell malignancies. 278 74

The effects of 1,25(OH)2D3 and dexamethasone on cellular proliferation and gene expression of the HTLV-I-infected T-cell line, KH-2, established from a patient with adult T-cell leukemia, endemic in the south-west Japanese islands and the Caribbean, were examined. KH-2 cells are integrated by HTLV-I proviral DNA and expressed mRNA for c-myc, IL-2 receptor alpha-chain (IL-2R alpha), and T-cell receptor beta-chain (TCR beta) while it did not express IL-2 mRNA. 1,25(OH)2D3 and dexamethasone did not suppress the mRNA levels of HTLV-I, IL-2R alpha or TCR beta but reduced the c-myc mRNA level. The reduction of c-myc mRNA level was marked in 1,25(OH)2D3-treated cells but relatively weak in dexamethasone-treated cells. This inhibitory effect of the steroid hormones correlated with the inhibition of KH-2 cell proliferation.
Int J Cancer 1989 Oct 15
PMID:Suppression of c-myc mRNA expression by steroid hormones in HTLV-I-infected T-cell line, KH-2. 279 41

Altered cellular immunity in patients with advanced head and neck cancer includes impairments in lymphokine production, blastogenesis, in vitro cytotoxicity, and T-cell levels. Recent evidence for the potential importance of in lymphokine interleukin 2 (IL-2) in patients with cancer prompted a study of the kinetics of IL-2 receptor expression on lymphocytes from patients with untreated advanced head and neck cancer and normal subjects and an evaluation of the in vitro effects of the T-cell immune-reconstituting peptide, thymosin alpha 1. Concanavalin A-stimulated IL-2 receptor expression was maximal after 72 hours and was higher in normal subjects than in patients. This was due to lower levels of helper/inducer (CD4) cells expressing IL-2 receptors in the patients compared with the normal subjects. Thymosin alpha 1 further decreased levels of IL-2 receptor-positive (both CD4 and CD8) cells at 48 and at 72 hours. At 96 hours, levels of IL-2 receptor-positive cells and proportions of cells in G2 and M phases of the cell cycle were similar among both groups of subjects. Simultaneous cell kinetic studies indicated that thymosin alpha 1 down regulation of IL-2 receptors was not due to an effect on proliferation and that differences in IL-2 receptor expression at 72 hours among normal subjects and the patients with cancer were more likely related to differences in cell proliferation kinetics.
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PMID:Interleukin 2 receptor expression in patients with head and neck squamous carcinoma. Effects of thymosin alpha 1 in vitro. 280 15

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.
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PMID:Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. 280 69

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.
Int J Cancer 1986 Aug 15
PMID:IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. 287 15

Cynomolgus monkeys and squirrel monkeys were inoculated with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I (HTLV-I) in order to serve as an animal model of adult T-cell leukemia (ATL). The autologous cell lines were established from peripheral blood mononuclear cells (PBMC) from each monkey by co-cultivation with lethally irradiated MT-2 cells producing HTLV-I. All of these cell lines, which had monkey karyotypes, grew continuously without addition of interleukin-2 (IL-2) and expressed virus-specific proteins of HTLV-I and IL-2 receptor. After inoculation with the autologous cell lines, specific antibodies against HTLV-I proteins could be detected in their plasma, and transformed HTLV-I-infected cells could be recovered from their peripheral blood for at least 6 months. However, no signs of ATL have been observed to data, i.e. 2 years after inoculation.
Int J Cancer 1986 Dec 15
PMID:Experimental inoculation of monkeys with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I. 287 91

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

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.
Jpn J Cancer Res 1988 May
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

There has been considerable effort in chemically conjugating a variety of plant and bacterial toxins to monoclonal antibodies that are directed to surface antigens on target cells. Coupling has been mediated through disulfide linkage, and the resulting conjugates are known generically as immunotoxins. In general, there are a few shortfalls to this approach. For example, since it is clear that not all surface antigens are internalized, one cannot predict the fate of a given IT once bound to its determinant on the surface of a target cell. In addition, in most instances one must activate the amino moiety of lysine residues with a heterobifunctional reagent in order to form disulfide linkage between the ligand and toxophore components. Since the number of reactive groups may be large, the disulfide linked conjugate molecules most likely represent a family of isomeric molecules rather than a defined protein. As a result, one cannot readily manipulate the fine structure of an IT in order to probe the mechanism of toxophore entry into the target cell. The approach that our group has taken toward the development of targeted cytotoxins, however, differs in a fundamental way: Rather than chemically coupling the ligand with toxophore through a disulfide bond, we have turned to genetic engineering in order to create gene fusions whose chimeric products are joined through a peptide bond. Thus, we have genetically constructed a family of fusion genes in which the receptor binding domain of diphtheria toxin has been deleted and replaced with DNAs encoding either alpha-MSH or IL-2. In each instance, it was known that the polypeptide ligand component of the fusion protein bound to specific receptors on target cells and was internalized by receptor mediated endocytosis. We reasoned, therefore, that the substitution of the diphtheria toxin receptor binding domain by these ligands should result in the formation of 'new' toxins whose action should be targeted toward selected eukaryotic cells that expressed either the alpha-MSH or IL-2 receptor. As along as the ligand component was exposed on the surface of the chimeric toxin, the molecule should bind to its receptor and be drawn into the cell by receptor-mediated endocytosis. Since the toxin-related/peptide hormone fusion protein is the product of a chimeric gene, it is a single molecular species. This has allowed us to begin to probe by site-directed mutagenesis the structure of fragment B sequences that are required to facilitate the translocation of fragment A across the target cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Treat Res 1988
PMID:Diphtheria-related peptide hormone gene fusions: a molecular genetic approach to chimeric toxin development. 290 22

From one colonic carcinoma chemically induced in the rat, 2 sublines of tumor cells have been cloned, one (PROb) inducing progressive tumors, the other (REGb) generating tumors that regress a few weeks after s.c. injection into syngeneic hosts. Our study was aimed at comparing cellular immunity between animals bearing PROb or REGb tumors. Spleen cells were first tested for in vitro proliferation in response to mitomycin-treated PROb or REGb cells. Only spleen cells from rats injected with REGb cells proliferated significantly when mixed with PROb or REGb cells. The proliferative response induced by REGb cells was considerably higher than the response to PROb cells. When spleen cells from rats bearing REGb tumors were cultured with a mixture of REGb and PROb cells at various PROb/REGb cell ratios, PROb cells significantly suppressed the strong proliferative response generated by the same number of REGb cells alone. REGb-immune spleen cells, after in vitro stimulation by PROb or REGb cells, were not cytotoxic for either cell variant. REGb-immune spleen cells did not differ in their content of T lymphocytes expressing CD4 or CD8 markers when they were stimulated by PROb or REGb cells in vitro, but REGb cells induced a larger number of activated lymphocytes expressing the IL-2 receptor. Our results indicate that, compared to REGb cells, PROb cells are poorer stimulators of proliferation of tumor-immune spleen cells, and that they are able to suppress the proliferative response induced by REGb cells.
Int J Cancer 1989 Feb 15
PMID:In vitro proliferative responses of spleen lymphocytes from rats bearing progressive or regressive tumors induced by cell variants of a syngeneic colon carcinoma. 291 5


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