Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of leukoregulin, a dominant tumor inhibitory lymphokine in native nonfractionated lymphokine preparations, was studied at the target cell level to ascertain its role as a molecular mediator in natural killer lymphocyte cytotoxicity. Leukoregulin was isolated from lymphokines produced by phytohemagglutinin stimulated human peripheral blood mononuclear leukocytes. Thirty minute leukoregulin treatment increased the sensitivity of human K562 leukemia cells to natural killer cell cytotoxicity. Maximum target cell sensitization to natural killer cytotoxicity was achieved within two hours. Measurement of K562 cell surface conformation by narrow angle forward light scatter and plasma membrane permeability by fluorescein diacetate fluorochromasia with a FACS IV flow cytometer demonstrated leukoregulin specific bio-membrane changes as early as five minutes with a maximum being attained within two hours of target cell exposure to leukoregulin. Analysis of K562 cells during development of a natural killer cell cytotoxicity reaction showed identical flow cytometric cell surface membrane changes to those developing in K562 cells exposed to leukoregulin alone. These observations suggest that leukoregulin is an intrinsic element in natural killer cell cytotoxicity and that the modulation of natural killer cell cytotoxicity may result from the early alteration in target cell surface membrane integrity induced by leukoregulin.
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PMID:Flow cytometric evaluation of leukoregulin as an intrinsic molecular mediator of natural killer lymphocyte cytotoxicity. 244 52

We have established an Ag-specific in vitro system for studying the roles of Ag and IL-5 in B cell differentiation and Ig production. The murine B cell leukemia, BCL1B1, was transfected with mu and kappa genomic sequences and VS107 V regions that conferred a T15 Id and phosphocholine-binding specificity upon the cells. Transfected cells were treated with both the T-dependent Ag phosphorylcholine-key-hole limpet hemocyanin (PC-KLH), and 0.5 ng/ml purified IL-5. After 3.5 days steady state mu-mRNA levels increased three- to fourfold over mu-mRNA levels obtained from untreated cultures, or cultures treated with IL-5 or PC-KLH alone. IL-5 alone caused increased Ig secretion and a nearly twofold increase in proliferation. Additionally, cells treated with PC-KLH alone were able to process the Ag and present it to T cells as shown by subsequent lymphokine production. Thus, both Ag and IL-5 used singly appear to interact with their respective receptors, although neither Ag nor IL-5 increased mu-mRNA levels when used singly. The production of increased mu-mRNA levels obtained with Ag plus IL-5 required polymerase II transcription, suggesting that they may act to increase Ig transcription directly.
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PMID:Induction of immunoglobulin mu mRNA in a B cell transfectant stimulated with interleukin-5 and a T-dependent antigen. 248 Mar 80

Two lymphokines that contribute to induction of cell differentiation in promyelocytic HL-60 leukemia cells by human T-cell lymphoma HUT-102 cells were identified previously. The lymphokines identified in the differentiation-inducing preparation were interferon-gamma (IFN-gamma) and lymphotoxin. To determine the remaining component(s) of this differentiation-inducing activity, we used gene-cloned (recombinant) forms and antibodies of lymphokines. The differentiation-inducing activity of the HUT-102 cells was not completely neutralized by the antibodies, suggesting that an additional lymphokine(s) is involved. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with retinoic acid induced differentiation of the HL-60 cells in a dose-dependent manner. Furthermore, the activity of the differentiation-inducing factors was partially inhibited by anti-GM-CSF antibody and completely inhibited by the combination of antibodies to lymphotoxin, IFN-gamma, and GM-CSF. These results indicate that, in addition to IFN-gamma and lymphotoxin, GM-CSF is the third major component released by HUT-102 cells for inducing differentiation of HL-60 cells.
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PMID:Identification of components of differentiation-inducing activity of human T-cell lymphoma cells by induction of differentiation in human myeloid leukemia cells. 249 90

Interleukin 2 (IL-2) is a secreted glycoprotein which acts as an activation and proliferative signal for lymphocytes expressing membrane-bound glycoprotein IL-2 receptors. We have recently established that swainsonine (SW), an inhibitor of mannosidase II during N-linked glycoprotein processing, augmented mitogen-induced mononuclear leukocyte IL-2 receptor expression and IL-2-induced proliferation. The objective of the present investigation was to examine the effect of SW on lymphokine-activated killer (LAK) cell induction. Human mononuclear leukocytes were treated with various concentrations of SW (0.1-10 micrograms/ml) and IL-2 (1-100 units/ml) for up to 72 h. SW augmented IL-2-induced LAK activity directed against human lung carcinoma, melanoma, and leukemia cells 2-3-fold. LAK activity generated in the presence of SW at suboptimal doses of IL-2 (10 units/ml) was similar to that observed with higher concentrations of IL-2 (100 units/ml) alone. SW treatment alone or in combination with IL-2 increased the percentage of IL-2 receptor-positive cells. Furthermore, pretreatment with SW subsequently enhanced IL-2-induced lymphocyte proliferation. SW-treated mononuclear leukocytes exhibited an increase in high-mannose type glycoproteins based upon [3H]mannose labeling, susceptibility to alpha-mannosidase, and binding to concanavalin A-Sepharose. These results indicate that modulators of glycoprotein processing may be useful in lowering the concentrations of IL-2 required for LAK induction and maintenance.
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PMID:Potentiation of human lymphokine-activated killer cell activity by swainsonine, an inhibitor of glycoprotein processing. 250 Oct 20

The induction of lymphokine-activated killer (LAK) cells against fresh human leukemia cells was investigated. Two thirds of the 62 leukemias examined were susceptible to the lytic effect of allogeneic IL-2 induced LAK cells in vitro. No substantial differences could be detected between myeloid or lymphoid leukemias or with regard to the FAB subtype or the immunophenotype. Culturing mononuclear cells from peripheral blood or bone marrow of leukemia patients with IL-2 resulted in an expansion of residual large granular lymphocytes and development of cytotoxic activity. The combination of IL-2 with IFN-gamma or the presence of tumor cells during the activation process led to an enhancement of LAK cell cytotoxicity. These results suggest that LAK cells may be useful in the treatment of leukemia.
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PMID:Induction of lymphokine-activated killer cell against human leukemia cells in vitro. 250 11

We have developed a series of human intrathyroidal T-T cell hybridomas and evaluated their phenotypic characteristics and lymphokine secretions in order to further understand the role of the T cell in Graves' disease. Mitogen-stimulated T cell blasts were generated from intrathyroidal lymphocyte preparations and fused with a hypoxanthine-, aminopterin-, and thymidine-sensitive variant of the Molt 4 human leukemia T cell line. The resulting intrathyroidal T-T cell hybridomas and T-T cell hybridomas obtained from normal peripheral blood mitogen-stimulated T cell blasts were expanded and tested for their biological function. None of the generated T cell hybridomas exhibited antigen-specific IL-2 secretion when stimulated with autologous thyrocytes, although 60% of the hybridomas expressed CD3 antigen and the T cell receptor alpha/beta heterodimer. However, 9 intrathyroidal and 11 peripheral blood T cell hybridomas secreted a factor(s) that significantly enhanced immunoglobulin G secretion in vitro (P less than 0.005, by Student-Newman-Keuls test; mean +/- SEM, 338 +/- 60% increase). In summary, we have successfully used a technique that allows the construction of T-T cell hybridomas derived from intrathyroidal T cell cultures. The data demonstrated that a predominance of helper factor-secreting T cells were available for fusion within the Graves' thyroid gland. Such observations are further evidence for intact T cell help within the thyroid gland of patients with Graves' disease.
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PMID:Successful production of intrathyroidal human T cell hybridomas: evidence for intact helper T cell function in Graves' disease. 253 Nov 54

Large granular lymphocytes (LGL) have been characterized phenotypically and functionally as cytotoxic T lymphocytes, NK cells or lymphokine-activated killer cells. The most prominent morphologic feature of LGL is large cytoplasmic granules that are thought to contain the molecules responsible for cell lysis. In this study, we describe the morphologic and functional characteristics of IL-2-dependent cytotoxic lymphocytes derived from feline PBL. Stimulation of feline PBL with Con A followed by culturing in 50 U of gibbon monkey IL-2 human rIL-2 induced long term lymphocyte cultures. These lymphocytes are cytotoxic for the feline leukemia virus-induced T cell lymphoma (FL74), in a 4-h 51Cr release assay. All cell lines are either constitutively cytotoxic for FL74 cells, or cytotoxic in a lectin-dependent cell cytotoxic assay, the latter being a characteristic of low passage cultures. In contrast, no cell lines express self lysis or lysis for other lines. [3H]TdR uptake showed that 1 U of human rIL-2 produces a 50% maximal proliferative response by feline lymphocytes suggesting a high degree of homology between the ligand binding sites of feline and human IL-2R. Feline cytotoxic lymphocytes possess abundant cytoplasm containing large azurophilic granules characteristic of LGL. These granules are bound by a bilipid membrane and contain numerous smaller membrane-bound vesicles 50 to 60 nm in diameter. A model is proposed, whereby subsequent to binding of LGL to target cell the large granules fuse to the LGL plasma membrane and release the small vesicles into the binding pocket. The vesicles then transport the lytic molecules directly and selectively to the target cell membrane.
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PMID:Feline cytotoxic large granular lymphocytes induced by recombinant human IL-2. 254 49

Immunization of C57BL/6 (B6) mice with FBL, a Friend murine leukemia virus (F-MuLV), induces both tumor-specific cytolytic CD8+ (CTL) and lymphokine-producing CD4+ Th that are effective in adoptive therapy of B6 mice bearing disseminated FBL leukemia. The current study evaluated the F-MuLV antigenic determinants expressed on FBL that are recognized by FBL-reactive CD8+ and CD4+ T cells. To identify the specificity of the FBL-reactive CD8+ CTL, Fisher rat embryo fibroblast (FRE) cells transfected with plasmids encoding F-MuLV gag or envelope (env) gene products plus the class I-restricting element Db were utilized. FBL-reactive CTL recognized FRE target cells transfected with the F-MuLV gag-encoded gene products, but failed to recognize targets expressing F-MuLV env. Attempts to generate env-specific CD8+ CTL by immunization with a recombinant vaccinia virus containing an inserted F-MuLV env gene were unsuccessful, despite the generation of a cytolytic response to vaccinia epitopes, implying that B6 mice fail to generate CD8+ CTL to env determinants. By contrast, CD4+ Th clones recognized FRE target cells transfected with env and not gag genes, and immunization with the recombinant vaccinia virus induced an env-specific CD4+ T cell response. These data show that in a Friend retrovirus-induced tumor model in which tumor rejection can be mediated by either CTL or Th, antigens derived from discrete retroviral proteins are predominantly responsible for activation of each T cell subset.
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PMID:FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens. 256 82

Clinical and experimental data suggest a role for the immune response in preventing leukemic relapses following allogeneic bone marrow transplantation the graft-versus-leukemia (GVL) effect. In the context of an allogeneic BMT, a number of different immune mechanisms mediated by donor cells may be responsible for the GVL effect. We have approached this question by using limiting dilution cultures of alloactivated human lymphocytes to analyze the in vitro allogeneic cytolytic response against fresh allogeneic leukemia. Initial results in the limiting dilution assays with split culture analyses demonstrated frequent alloreactive cytolytic T lymphocyte precursors that destroyed remission peripheral blood lymphocytes and leukemic cells from the allogeneic leukemic patient. These assays also demonstrated frequent lymphokine-activated killer (LAK) cell precursors that lysed both the LAK sensitive Daudi line and the allogeneic leukemia. In these experiments, isolated cultures also showed cytolytic activity directed against the allogeneic leukemic blasts without activity against remission PBL, or the LAK-sensitive Daudi cell line. Two T cell lines (ABL1 and ABL2) isolated from an LDA, demonstrated this form of specificity, mediating destruction specifically against the allogeneic acute lymphoblastic leukemic cells. Both cell lines ABL1 and ABL2 were CD3+, TCR alpha beta +, and CD4+. These 2 cell lines mediated little or no cytotoxicity against a large panel of other targets tested (natural killer sensitive and resistant cell lines, allogeneic PBL, and allogeneic fresh leukemic blasts). Antibody-blocking experiments revealed a role for the CD3-TCR receptor of both cell lines in lysis of leukemic cells; the CD4 and MHC class II molecules were clearly involved in the lysis by the ABL1 cell line. Specificity of recognition for the allogeneic leukemic blasts was further confirmed by unlabeled target competitive inhibition studies. The mechanism of the preferential lysis of leukemia by the alloactivated T cell lines described in this paper remains uncertain. Nevertheless, these leukemic-specific populations provide a means by which the human GVL effect may be further studied in vitro.
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PMID:Specific recognition of human leukemic cells by allogeneic T cell lines. 257 Dec 6

Mast cells (MC) are regular constituents of soft tissue and occur with varying frequency in nearly every organ. They derive from monocytic cells occurring in the adhering mononuclear fraction of the peripheral blood. Their subsequent evolution into mature MCs is primed by a MC generating lymphokine released by sensitized T-cells on restimulation by the antigen. MC granules contain preformed heparin histamine and eosinophil chemotactic factors. Other factors such as leukotriene B4 can be produced by MCs following stimulation. This is the case during the initial phase of nonspecific inflammations, when MCs are stimulated by complement activation. In the immediate type hypersensitivity reaction giving rise to IgE, MC degranulation occurs independent from complement. In IgG and IgM mediated reactions, however, MC involvement is effected by complement consumption and C5 a generation. In delayed type hypersensitivity MCs increase locally. Their functional significance remains obscure. MC neoplasias are rare and generally confined to the dermis. Cutaneous mastocytoses are called benign mastocytoma when localized and urticaria pigmentosa when disseminated. Generalized mastocytosis involves extracutaneous tissue irrespective of skin involvement. Those associated with urticaria pigmentosa-like skin lesions, present at the onset of the disease, have a significantly higher survival rate than those lacking a primary skin involvement. The term urticaria pigmentosa should be reserved for cases of cutaneous mastocytosis without extracutaneous involvement. Cases of mastocytoses lacking primary skin lesions assume a malignant course and are additionally aggravated by high incidence of myeloproliferative disorders and MC leukemia. MC sarcoma is an extremely rare neoplasia of MCs which may also terminate as a MC leukemia.
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PMID:Tissue mast cells in health and disease. 258 3


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