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

Murine splenocytes immune to influenza virus-activated human T-cells were fused with SP2/0 cells, selected in chemically defined HAT media, and subcloned to yield a monoclonal antibody (MAb) termed 7G7/B6. 7G7/B6 binds to lectin- and antigen-activated T-cells, but not resting T-cells or B-lymphoblastoid lines from the same donor. 7G7/B6 immunoprecipitates a 50-55 kD band from cell surface iodinated PHA-activated T-cells or the T-cell leukemia line HUT 102B2, as shown on SDS-PAGE. Cross-clearing studies demonstrate that 7G7/B6 binds the same cell surface molecule(s) as anti-Tac, a MAb which has been shown previously to recognize the human receptor for IL-2. 35S-methionine pulse chase experiments in HUT 102B2 cells reveal that 7G7/B6 binds to an early (less than 30 min) 35-37 kD and late (greater than 4 h) 50 kD protein. Sequential immunoprecipitations demonstrate that these are identical to the molecules identified by anti-Tac under similar conditions. However, only anti-Tac coprecipitates a higher molecular band at 110 kD. 7G7/B6 and anti-Tac do not competitively inhibit the binding of each other to PHA-activated T-cells. Functional studies reveal that in contrast to anti-Tac, 7G7/B6 has almost no inhibitory effect in vitro on IL-2-driven proliferation of IL-2-dependent T-cell lines, or alloimmune cytotoxic T-cell generation (however, once generated, these cytotoxic T-cells were both 7G7/B6 and anti-Tac positive). Finally, IL-2 does not inhibit the binding of 7G7/B6 to activated T-cells under conditions which result in up to 75% inhibition of anti-Tac binding. Therefore, 7G7/B6 is another MAb recognizing the human IL-2 receptor, but binding to an epitope distinct from that recognized by either IL-2 or anti-Tac.
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PMID:A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. 240 92

A variant of the Jurkat leukemia cell line termed JA3 (surface phenotype: T11+., T3+, T4-, T8-, T6-, T1+, 3A1+, HLA-DR-, Tac-, 4F2+) has been used for mouse immunization and production of monoclonal antibodies (MAbs) to molecules carrying clonotypic determinants that are thought to serve as receptor for antigen on human T cells. JA3 had been selected because of its ability to release large amounts of IL-2 following stimulation with phytohemagglutinin (PHA) or anti-T3 antibody in the presence of phorbolmyristate acetate (PMA). This functional property has been exploited for screening of MAbs potentially directed to idiotype-like structures of JA3 cells. Thus supernatants of hybridomas (obtained by fusing mouse splenocytes with P3-UI myeloma cells) were analyzed for their ability to induce JA3 cells to release IL-2 in the presence of PMA. Four stimulatory antibodies reacted with JA3 but not with polyclonal T-cell populations, T-cell clones, or T and B tumor cell lines as assessed by indirect immunofluorescence and fluorescence-activated cell sorter (FACS) analysis. All 4 antibodies immunoprecipitated the same disulphide-linked heterodimeric molecules having a molecular mass (Mr) of approximately 85,000 under non-reducing conditions that was resolved in 2 major peptides of 40,000 and 45,000 under reducing conditions. These data indicate that these antibodies (termed anti-JTi) were directed to the clonotypic-restricted structures of the JA3 T-cell-receptor molecules. Unlike the anticlonotypic antibodies described so far, anti-JTi MAbs were capable of triggering IL-2 production even in unbound, soluble form, in the absence of adherent cells or PMA. Competitive inhibition experiments, in which 35S-labelled anti-JTi MAbs have been used, provided evidence that they may be directed against different epitopes on the same clonotypic structure.
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PMID:Selection and characterization of monoclonal antibodies to the idiotype-like structure of an interleukin-2-producing human leukemia T-cell line. 241 Mar 77

The ability of alloimmune spleen cells expanded in mixed leukocyte culture (MLC) and cloned cytotoxic T lymphocytes (CTL) to kill H-2-compatible leukemia in vivo was evaluated. In comparison with fresh alloimmune spleen cells, MLC-expanded cells had a significantly higher frequency of CTL reactive against leukemia targets in vitro. However, the reactivity of MLC-expanded cells against first-passage spontaneous AKR (H-2k) leukemia in vivo was significantly less than when an equivalent number of fresh alloimmune spleen cells was injected. Comparable antileukemia reactivity was observed in vivo only when the inoculum of MLC-expanded cells was 2-3-fold higher than that of fresh spleen cells. This relative ineffectiveness was attributed to the altered migration pattern of cultured cells in vivo. IL-2-dependent cloned CTL, specific for a normal lymphocyte antigen (Qa-1b) also present on leukemia cells, were derived from MLC-expanded cultures and tested in vivo. For cloned CTL, as with MLC-expanded cells, eradication of AKR leukemia in vivo was associated with the tissue distribution pattern of the injected effector cells. That is, an effective antileukemia reaction was achieved only in tissues in which effector and target proximity was maintained. Qa-1b-specific cloned CTL did not interfere with engraftment of autologous or allogeneic bone marrow in lethally irradiated host mice, nor did they cause any clinically evident graft-versus-host disease. These findings suggest that cloned CTL specific for a normal cell surface antigen with limited host tissue distribution, but present on tumor cells, could be used for adoptive immunotherapy, provided CTL and tumor cell proximity can be attained.
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PMID:Reactivity of in-vitro-expanded alloimmune cytotoxic T lymphocytes and Qa-1-specific cytotoxic T lymphocytes against AKR leukemia in vivo. 241 69

A human eosinophilic leukemia cell line, designated as EoL, was established from the peripheral blood of a patient with Philadelphia chromosome-negative eosinophilic leukemia (EL). The EoL cell line grows in single cell suspension with a doubling time of 48 hours for about one year. The reactivity of these cells was tested with a panel of monoclonal antibodies; they were found to express surface IA antigen, myeloid antigen (IF10, MY9) and membrane receptors for interleukin 2 (IL-2, Tac antigen). Under standard culture conditions, a small percentage of cells having more typical eosinophilic characteristics was present. These cells had cytoplasmic granules and were positive for Luxol-fast-blue and eosinophil peroxidase. Under culture conditions to induce the maturation of myeloid cells, such as alkaline medium or addition of dimethyl sulfoxide (DMSO), the frequency of cells with typical eosinophilic features increased to about 40%. In addition, cytogenetic studies showed that cultured cells and original leukemic blasts presented similar chromosome abnormalities. EoL seems to be a unique leukemic line committed to the eosinophilic lineage and can provide a useful in vitro model for the study of malignant eosinophilic properties.
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PMID:Establishment and characterization of a new human eosinophilic leukemia cell line. 241 85

Phosphotyrosine antibodies were employed to immunodecorate and immunoprecipitate proteins phosphorylated at tyrosine residues in cells transformed by Abelson murine leukemia virus (A-MuLV). In pre-B and pre-T lymphoma cells transformed by A-MuLV, the major phosphotyrosine-containing protein has an MW of 160 kDa and shares immunologically detectable sequences with the v-abl oncogene product. Moreover, two different proteins of approximately 100 and 68 kDa, heavily phosphorylated at tyrosine, were identified. Lack of immunological cross-reactivity with viral products and phosphopeptide mapping showed that the 100 and 68 kDa proteins are coded by cellular genes. Phosphoproteins were undetectable in control resting lymphocytes. The 68 and the 100 kDa proteins were phosphorylated to different extents in proliferating lymphocytes, either stimulated by the growth factor IL-2, or transformed by M-MuLV (lacking the oncogene coded kinase). In fibroblasts transformed by A-MuLV, phosphotyrosine antibodies identified 2 proteins of 120 and 70 kDa. By immunological cross-reaction and by phosphopeptide mapping, the first was identified as a 120 kDa form of the v-abl coded kinase. The 70 kDa protein is coded by a cellular gene, is not structurally related to the 120 kDa v-abl kinase, and is different from any phosphotyrosine-containing protein detected in A-MuLV-transformed lymphocytes. These data show that, upon v-abl-induced transformation, phosphorylation at tyrosine takes place also on proteins other than the 160 or 120-kDa oncogene products. In lymphocytes and fibroblasts these proteins are different, suggesting that the cascade of events triggered by the v-abl gene in different cell types involves tyrosine phosphorylation of different specific proteins.
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PMID:Protein phosphorylation at tyrosine residues in v-abl transformed mouse lymphocytes and fibroblasts. 242 Jul 27

It is known that IL-2 induces lymphocytes to produce interferon-gamma (IFN-gamma) and this IFN type is particularly efficient in inducing tumor cell resistance to natural killer (NK) cell-mediated lysis. We have investigated the effect of IFN on tumor cell sensitivity to LAK cell-mediated cytotoxicity. Pretreatment of the human K562 leukemia and HHMS melanoma with IFN-gamma and the Daudi lymphoma with IFN-alpha caused a significant reduction in sensitivity to lysis by human LAK cells generated in vitro in the presence of human recombinant IL-2 (100 U/ml). The LAK activity was mediated by cells expressing NK cell markers (CD16,NKH1) as well as by cells with T cell markers (CD3, CD5). IFN-treated K562 cells were protected from lysis mediated by all these populations. Supernatants from LAK cultures containing IFN-gamma were able to induce NK and LAK resistance when used to pretreat K562 overnight. Antibodies to IFN-gamma but not to IFN-alpha were able to neutralize this activity. Taken together, these results indicate that the production of IFN-gamma by LAK cells may be of importance in induction of tumor cell resistance to LAK cell-mediated lysis.
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PMID:Interferon is able to reduce tumor cell susceptibility to human lymphokine-activated killer (LAK) cells. 246 94

The purpose of this study was to examine the role of IL-1 on the activation of CD8+/CD4- class I-restricted helper cell-independent cytolytic T cell (HITc) clones known to produce IL-2 and proliferate in vitro after Ag stimulation with a Friend retrovirus-induced leukemia (FBL). The functional role of IL-1 in Ag-specific proliferation and IL-2 secretion was assessed by stimulating the T cell clones with FBL either in the presence or absence of macrophages (M phi), rIL-1, or rIL-2. Resting cloned HITc cells, purified from residual accessory cells, failed to proliferate in response to FBL alone, but proliferated in response to FBL plus M phi, rIL-1 or rIL-2. Stimulation with FBL alone in the absence of M phi or IL-1 was sufficient for induction of IL-2R expression, and rendered cells responsive to IL-2, but M phi or IL-1 were also required to induce production of IL-2. The activity of IL-1 was further examined by measuring the binding of [125I]rIL-1 alpha, which demonstrated that resting cloned HITc cells expressed IL-1R that increased in number after activation with Ag. This expression of IL-1R and requirement for IL-1 by CD8+ HITc was surprising because previous studies examining T cell populations after mitogen stimulation have not detected IL-1R on the CD8+ population. Therefore, the role of IL-1 in the activation of CD8+ CTL that do not secrete IL-2 after activation was assessed. By contrast to HITc, CD8+ CTL required exogenous IL-2 to proliferate in vitro and did not express IL-1R. These data demonstrate that the subset of CD8+ T cells responsible for IL-2 production express IL-1R and that triggering this receptor with IL-1 after Ag stimulation results in the production of IL-2 and subsequent proliferation.
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PMID:Helper-independent CD8+ cytotoxic T lymphocytes express IL-1 receptors and require IL-1 for secretion of IL-2. 246 90

The evidence that schizophrenia may involve infection by a virus (or viruses) has been indirect. The recent discovery, however, of the human retroviruses--human T-cell lymphoma-leukemia virus-I, and II (HTLV-I, -II) and human immunodeficiency virus (HIV)--now also known to affect the central nervous system (CNS), together with the development of new techniques in retrovirology, have made it possible to investigate more directly the role of this class of viruses as an etiology of schizophrenia. In our first effort to screen for the presence of a T-cell lymphotropic virus in schizophrenia, short-term tissue cultures of peripheral lymphocytes from 17 chronic schizophrenic patients and 10 normal controls were established. The cells were cultured in the presence of T-cell growth factor (TCGF, IL-2), and the culture supernatants were tested for the presence of the retroviral enzyme reverse transcriptase. No T-cell-associated reverse transcriptase activity was detected in cultures from patients or normal controls. Therefore, the data do not provide evidence for a role for T-cell lymphotropic retroviruses as an etiology of schizophrenia.
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PMID:Lack of evidence for a role of T-cell-associated retroviruses as an etiology of schizophrenia. 246 91

Recent progress in biotechnology has uncovered the presence of trace substances which participate in the immunological response between cancer and host; They are cytokines, monoclonal antibodies, and immunomodulating agents produced by effector cells which are called macrophage, NK cells and lymphocytes of cancer patients. Recent genetic engineering enables mass production of these substances, and their clinical application in treating human cancers is expected to take place in the near future. In this paper, the recent trend of cancer treatment, using various cytokines are briefly introduced, namely interferon, interleukin-2, tumor necrosis factor and colony stimulating factor. Although IL-2 is effective for the activation of T-lymphocyte, intravenous injection of IL-2 is not so effective for treatment of cancer-patients. On the other hand, IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. The clinical study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration. Tumor necrosis factor, a cytotoxin derived from macrophages shows much promise for application in cancer therapy because of its marked antitumor effects and its high specificity to tumors. Clinical study was performed on leukemia patients who showed marked decreases of percentage of leukemic cells in peripheral blood. Moreover, local injection of TNF was very effective for the decrease of tumor size in patients with hepatoma and subcutaneous tumor. In addition, to clinical results using CSF and interferon are reported.
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PMID:[Recent trends in cancer treatment using cytokines]. 247 55

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


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