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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 have earlier observed that 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), a chemotherapeutic drug, cured 90-100% of mice bearing a syngeneic Ia- T-cell lymphoma (LSA) and furthermore, 100% of the BCNU-cured mice could reject homologous tumor rechallenge. In the present study, purified CD4+ and CD8+ T cells isolated from BCNU-cured mice were used to investigate the mechanism by which such T cells recognized and responded to the tumor-specific antigens. The responsiveness of CD4+ T cells to LSA was dependent on processing and presentation of tumor-specific antigens by syngenic Ia+ splenic antigen-presenting cells (APC). Such activated CD4+ T cells endogenously produced IL-2 but not IL-4 and only IL-2 acted as an autocrine growth factor inasmuch as anti-IL-2 receptor antibodies but not anti-IL-4 antibodies inhibited the CD4+ T cell proliferation. In contrast, the CD8+ T cells failed to produce endogenous growth factors when stimulated with LSA alone or with LSA plus APC, and therefore failed to proliferate. However, in the presence of exogenous recombinant IL-2 (rIL-2), CD8+ T cells could proliferate directly in response to LSA-stimulation, even in the absence of APC. Addition of exogenous rIL-4 alone to cultures induced CD4+ but not CD8+ T cells to proliferate. However, rIL-4 in the presence of rIL-2, could synergize and induce tumor-specific proliferation of CD8+ cells. These data suggested that for IL-4 to act as a T-cell growth factor, the presence of IL-2 was essential, either in the form of endogenously secreted IL-2 (CD4+ T cells) or exogenous IL-2 (for CD8+ T cells). In contrast to rIL-2 and rIL-4, rIL-6 failed to induce growth when used alone or in combination with rIL-2 or rIL-4. Furthermore, when tested individually, only rIL-2 but not rIL-4 or rIL-6 could support the cytotoxic differentiation of CD8+ T cells. The present study suggests that the early events in responsiveness to LSA tumor may involve activation of the IL-2-producing Th1 subpopulation of CD4+ helper cells which in turn activate IL-2 dependent CD8+ cytotoxic T cells. IL-4 if produced subsequently, may act synergistically with IL-2 to promote the growth of CD4+ and CD8+ T cells.
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PMID:Role of IL-2, IL-4 and IL-6 in the growth and differentiation of tumor-specific CD4+ T helper and CD8+ T cytotoxic cells. 197 41

The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor.
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PMID:Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. 205 45

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

A bovine papilloma virus-derived vector was used to direct the high level expression in mouse C127 cells of three different cDNAs encoding the human interleukin-2 receptor. These were: the previously described cDNA clone isolated from the T-cell lymphoma, HUT-102; a cDNA clone isolated from mitogen-activated, normal peripheral blood T cells; and an altered version of the HUT-102 receptor in which Ser247, believed to be the site of protein kinase C-mediated phosphorylation, has been changed to an Ala residue. Fluorescence-activated cell-sorting using a monoclonal antibody directed against the human IL-2 receptor was used to derive stable lines of C127 cells expressing from 2-6 X 10(6) IL-2 binding sites per cell. However, all of these receptors bound IL-2 with low affinity.
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PMID:High level stable expression of human interleukin-2 receptors in mouse cells generates only low affinity interleukin-2 binding sites. 309 20

Interleukin-2 (IL-2) receptor expression is a feature of T-cell activation and T-cell neoplasia. Expression of the IL-2 receptor in human lymphoid lesions was studied in a series of 166 immunophenotyped cases, including nodal and extranodal reactive lymphoid proliferations (44 cases), low-grade B-cell lymphomas (27 cases), intermediate and high grade B cell lymphomas (42 cases), peripheral T-cell lymphomas (13 cases), Hodgkin's disease (12 cases), histiocytic proliferations (15 cases), nonhematopoietic tumors (16 cases), and miscellaneous lesions (7 cases). Low levels of receptor expression were seen in reactive lymphoid lesions, low-grade B-cell lymphomas, and nonhematopoietic tumors (20%, 7%, and 25% of cases, respectively, with greater than 10% positive cells). High levels of receptor expression were seen in cases of peripheral T-cell lymphoma and histiocytic proliferations (86% and 100% of cases, respectively, with greater than 10% positive cells). Intermediate levels of expression were seen in Hodgkin's disease (including Reed-Sternberg cells) and some cases of intermediate and high-grade B-cell lymphomas (58% and 50% of cases, respectively, with greater than 10% positive cells). IL-2 receptor expression is not confined to T-cell neoplasia, but is also a feature of neoplastic and nonneoplastic histiocytic proliferations, Hodgkin's disease, and some intermediate and high-grade B-cell lymphomas. Biologic and therapeutic implications are discussed.
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PMID:IL-2 receptor expression in human lymphoid lesions. Immunohistochemical study of 166 cases. 310 54

The ability of tumor cells to produce and to respond to their own growth factor (autocrine secretion) may be of importance for their growth. We describe a human tumor cell line regulated by an autocrine secretion of the growth factor interleukin 2 (IL-2). This T-lymphocyte cell line, IARC 301, was established from a patient with a T-cell lymphoma in the absence of any added specific growth factor. It constitutively expresses biologically functional high-affinity cell-surface receptors for IL-2 as shown by the binding of both radiolabeled purified IL-2 and monoclonal antibodies to IL-2 receptors. In addition, it synthesizes IL-2, which is bound to cell surface receptors. Monoclonal antibodies directed against either IL-2 or the IL-2 receptor block IARC 301 cell growth. These findings demonstrate that the proliferation of this tumor cell line is mediated by an autocrine pathway involving endogenous IL-2 production and its binding to cell surface receptors.
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PMID:Autocrine growth stimulation of a human T-cell lymphoma line by interleukin 2. 393 Oct 81

T lymphocytes, essential for the generation of a normal immune response, require the presence of the lymphokine interleukin-2 (IL-2) in order to proliferate. Cells that respond to IL-2 possess a surface receptor glycoprotein specific for this lymphokine. We have recently purified and chemically characterized the IL-2 receptor from both phytohaemagglutinin-activated human T cells and the human T-cell lymphoma HUT-102 (ref. 5). From the NH2-terminal protein sequence obtained in that study, we have now used synthetic oligonucleotides to probe a complementary DNA library, prepared from HUT-102 messenger RNA, for the presence of cDNA clones that might code for the IL-2 receptor. Two cDNA clones were isolated which had closely related DNA sequences. Interestingly, only one coded for an active receptor when transfected into COS-7 cells. This clone contained a 216-base pair (bp) insert that was not present in the other clone. The insert was flanked by an 8-bp direct repeat reminiscent of a transposable element, and appeared to code for a region of marked structural homology to the NH2-terminal region of the receptor molecule.
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PMID:Cloning, sequence and expression of human interleukin-2 receptor. 609 20

Fusion of the YACUT T-cell lymphoma with the Mls-1a-antigen-specific non-tumorigenic T-cell line G4 was previously reported to produce growth-arrested hybrids that could be induced to proliferate in the presence of Mls-1a antigen. The proliferation-suppressed hybrid lines exhibited phenotypic changes as follows: the usually high levels in YACUT of J11d antigen, IL-2 receptor, and c-myb expression, which are markers of immature T cells, were all down-regulated; the G4 T-cell function, i.e., contact helper activity for B-cell proliferation in T/B cell collaboration, was retained. Furthermore, fusion of the YACUT lymphoma with a killer T-cell line produced growth-arrested and tetraploid somatic cell hybrids having killer activity. Thus, in addition to the transformed phenotype (autonomous proliferation in vitro), the antigen-specific non-tumorigenic T-cell line genomes introduced into the YACUT lymphoma suppressed the immature phenotypes of YACUT and imposed their own programming of terminally differentiated traits on the hybrids. Prolonged growth of the proliferation-suppressed hybrid lines by repeated antigenic stimulation was previously reported to result in the appearance of transformed hybrids, which was accompanied by both a reversion of c-myc expression to the levels of YACUT and an increase in the number of chromosome 15. The present study revealed that the amplification of chromosome 15 resulted from the duplication of the tumour-derived chromosome 15 carrying the rearranged pvt-1 gene. However, the differentiated phenotypes of the hybrids remained mostly unchanged upon cell transformation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of duplication of tumour-derived chromosome 15 carrying the rearranged pvt-1 gene in the transformed phenotype of YACUT T-cell lymphoma x G4 T-cell line somatic cell hybrids in dictating the terminal differentiation program of the parental G4 cell. 787 44

Autocrine stimulation is described for a Radiation leukaemia virus (RadLV)-induced T-cell lymphoma, C6VL/1. The proliferation of this tumour cell line can be regulated by several agents, including interleukin-2 (IL-2), antibodies to the IL-2 receptor and the T-cell antigen-specific receptor (TCR), as well as RadLV retrovirus particles produced by the cell itself. This information has been gained using various procedures to slow or arrest C6VL/1 proliferation, including the addition of gamma interferon (gamma-IFN) and cell culture at low density. All data suggest that these cells can receive growth stimulation via the T-cell receptor (TCR) and IL-2 receptor, implicating autocrine stimulation of growth involving IL-2 and retroviral gene products.
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PMID:Growth regulation of a T-cell lymphoma via the T-cell receptor. 828 63

In the current study, we investigated the role of interleukin-2 (IL-2) and IL-4 as autocrine growth factors responsible for autonomous growth of four murine tumor cell lines: LSA, a radiation leukemia virus-induced T-cell lymphoma; EL-4, a chemically triggered T-cell lymphoma; PE-3T, a T-cell line that underwent spontaneous transformation ex vivo; and P815, a mastocytoma. All tumor cell lines screened constitutively expressed IL-2 receptor (IL-2R) and IL-4R genes. However, only LSA and PE-3T cells expressed IL-2 and IL-4 genes constitutively, whereas EL-4 and P815 tumor cells expressed only IL-4 but not IL-2. Monoclonal antibodies (MoAbs) against IL-2, IL-4, or a combination of these, as well as MoAbs against IL-2R significantly inhibited the proliferation of LSA but not that of other tumor cell lines ex vivo. To exclude the possibility that, in other tumor cell lines, the autocrine growth factor may interact with its receptor within the cell, the ability of antisense phosphorothioate oligonucleotides to inhibit the growth of the tumor cells was tested. The antisense phosphorothioate oligonucleotides specific for IL-2, IL-4, IL-2R beta, or IL-2R gamma chains, added in culture, could markedly inhibit the growth of LSA but not that of the other tumor cell lines screened. Inasmuch as IL-2R beta and IL-2R gamma subunits also serve as a component of the receptors for IL-4, IL-7, IL-9, and IL-15, the above data suggested that such cytokine redundancy was not responsible for autonomous growth of the other tumor cell lines. Addition of exogenous IL-2 or IL-4 to the tumor cell cultures caused significant enhancement in the proliferation of PE-3T cells, whereas other cell lines were either not significantly affected or slightly inhibited from growing. Interestingly, the LSA tumor growth in nude mice was significantly inhibited after treatment of these mice with a combination of MoAbs against IL-2 and IL-4. Together, our studies show for the first time that IL-2 and IL-4 may serve as autocrine growth factors in the autonomous proliferation of tumor cells, particularly those that are retrovirally induced. Second, some tumor cell lines, despite expressing certain cytokines and their receptors constitutively, may not depend exclusively on such factors for autocrine growth.
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PMID:Evidence for the participation of interleukin-2 (IL-2) and IL-4 in the regulation of autonomous growth and tumorigenesis of transformed cells of lymphoid origin. 900 65


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