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)

Retrovirus infection of murine fibroblasts was found to alter the expression of major histocompatibility complex (MHC) antigens. Fibroblasts infected with Moloney murine leukemia virus (M-MuLV) exhibited up to a 10-fold increase in cell surface expression of all three class I MHC antigens. Increases in MHC expression resulted in the increased susceptibility of M-MuLV-infected cells to lysis by allospecific cytotoxic T lymphocytes (CTL). M-MuLV appears to exert its effect at the genomic level, because mRNA specific for class I antigens, as well as beta 2-microglobulin, show a fourfold increase. Fibroblasts infected with the Moloney sarcoma virus (MSV):M-MuLV complex show no increase in MHC antigen expression or class I mRNA synthesis, suggesting that co-infection with MSV inhibits M-MuLV enhancement of MHC gene expression. Quantitative differences in class I antigen expression on virus-infected cells were also found to influence the susceptibility of infected cells to lysis by H-2-restricted, virus-specific CTL. Differential lysis of infected cells expressing varied levels of class I antigens by M-MuLV-specific bulk CTL populations and CTL clones suggests that individual clones may have different quantitative requirements for class I antigen expression. The MSV inhibition of MHC expression could be reversed by interferon-gamma. Treatment of MSV:M-MuLV-infected fibroblasts with interferon-gamma increased their susceptibility to lysis by both allogeneic and syngeneic CTL. The data suggest that interferon-gamma may function in the host's immune response to viral infections by enhancing MHC antigen expression, thereby increasing the susceptibility of virus-infected cells to lysis by H-2-restricted, virus-specific CTL.
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PMID:Retrovirus-induced changes in major histocompatibility complex antigen expression influence susceptibility to lysis by cytotoxic T lymphocytes. 241 92

The influence of in vivo application of recombinant interferon-alpha 2c (IFN-alpha 2c) and recombinant interferon-gamma (IFN-gamma) on beta-2 microglobulin levels was studied in eight patients with chronic myelogenous leukaemia or advanced renal cell carcinoma. Data indicated enhanced beta-2 microglobulin biosynthesis in close temporary association with injection of both types of interferons. The influence of in vivo stimulation by allogenic leukocytes and the influence of renal allografts or cytomegalovirus infection on serum beta-2 microglobulin and IFN-gamma levels were also studied. Increased beta-2 microglobulin concentrations were observed again in each of these clinical situations and were closely associated with enhanced endogenous interferon production. From these in vivo data and the in vitro data presented in the preceding publication, (1) we conclude that endogenous interferon levels are crucial for the regulation of beta-2 microglobulin release in vivo.
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PMID:Cytokines in the control of beta-2 microglobulin release. II. In vivo studies with recombinant interferons and antigens. 245 79

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 ability of splenic T-cells to regulate Friend murine leukemia virus replication in lipopolysaccharide-activated target B-cells infected in vitro was investigated. Removal of the T-cell fraction from spleen cells resulted in an 8- to 10-fold enhancement in the number of productively infected cells in the remaining B-cell-enriched fraction, as compared with unseparated spleen cells, and the addition of increasing numbers of purified T-cells to isolated B-cells prior to infection resulted in a directly proportional reduction in the number of B-cells releasing infectious progeny virus. Separation of splenic T-cells into Lyt 2- and Lyt 2+ T-cells before addition to infected B-cell cultures resulted in inhibition of infection only with the Lyt 2- T-cells; Lyt 2+ T-cells did not inhibit infection, even at high 1:1 ratios. Similarly, separation of splenic T-cells into L3T4+ and L3T4- T-cells before addition resulted in inhibition by L3T4+ but not L3T4- T-cells. Also, cytotoxic treatment of splenic T-cells with monoclonal anti-L3T4 antibody and complement before addition to B-cell cultures destroyed the regulatory effects. Finally, depletion of macrophages from both T-cells and B-cells before infection and coculture had no effect on the ability of T-cells to regulate B-cell infection. Collectively these results demonstrate that L3T4+ T-cells can inhibit Friend murine leukemia virus replication in target B-cells. Culture of isolated splenic T-cells with Friend murine leukemia virus in vitro resulted in the induction of alpha/beta but not interferon-gamma synthesis and in some experiments interferon-containing supernatants from T-cell-virus cultures were able to mediate suppression of B-cell infection with Friend helper virus; the addition of antibody specific for interferon-alpha/beta to cultures inhibited the ability of T-cells to regulate B-cell infection.
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PMID:T-cells inhibit Friend murine leukemia virus infection of B-cells in vitro. 247 May 14

Delayed-type hypersensitivity (DTH) to Rauscher murine leukaemia virus (R-MuLV) encoded or induced determinants was induced in mice by three syngeneic R-MuLV-induced tumour cell lines, i.e. a myeloid tumour, RMB-1, an erythroid tumour, RED-1, and a lymphoid tumour, RLD-1. DTH to subcutaneously (s.c.) administered RMB-1 cells appeared on day 4, with a maximum DTH response on day 6 or 7. The induction of DTH could be prevented by intravenous (i.v.) pre-immunisation with R-MuLV-induced tumour cells several days before the s.c. immunisation. The three R-MuLV-induced tumour cell lines showed cross-reactivity in the DTH assay, whereas no cross-reactivity was found with syngeneic WEHI-3 cells. This indicates that the three R-MuLV-induced tumour cell lines share a virally encoded or induced antigenic determinant, which activates T-cells. When the RMB-1 cells used for immunisation had been cultured in medium supplemented with interferon-gamma (IFN-gamma), the subsequent DTH response was increased. This coincided with an increased expression of the R-MuLV-specific antigenic determinants on RMB-1 cells as demonstrated by Scatchard analysis. Furthermore, IFN-gamma increased the MHC class I antigen expression on RMB-1 cells, whereas the class II antigen expression remained undetectable.
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PMID:Enhancement and suppression of DTH reactivity to Rauscher murine leukaemia virus induced tumour cell lines. 247 52

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

The effects of interferon-gamma (IFN-gamma) on protein synthesis of a pre-B cell leukemia, L1210, have been studied by two-dimensional gel electrophoresis. In total cell extracts, at least ten proteins were induced de novo, or increased in their expression, after an 18-h IFN-gamma treatment, whereas in the nuclear extracts eight proteins were specifically induced. Of these, increased synthesis of a 40-kDa/pI 5.9 cytoplasmic protein was the most prominent and reproducible. Most of these proteins appear to be specific for a defined step of differentiation, since they are not found in other B cell leukemias upon IFN-gamma treatment. Others appear to be tissue specific, since they are not induced in fibroblasts nor in T cells. In addition, synthesis of some of the induced proteins appeared to require rapid transcription of new mRNA, because actinomycin D markedly inhibited their formation when added immediately before IFN-gamma. In keeping with this finding, in vitro translation of mRNA from IFN-gamma-treated L1210 cells into a rabbit reticulocyte lysate system, followed by analysis of the labeled proteins by two-dimensional gel electrophoresis, revealed the appearance of at least seven proteins. Taken as a whole, these results demonstrate that in leukemic pre-B cells IFN-gamma induces the transcriptional activation of genes coding for cytoplasmic and nuclear proteins, some of which could be employed as specific cell activation markers.
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PMID:Characterization of cytoplasmic and nuclear polypeptides induced by interferon-gamma in a murine pre-B cell leukemia. 250 85

The effects of the tumor necrosis factor (TNF), and a second pleiotropic cytokine interferon-gamma (IFN), were examined in a line of human myeloblastic leukemia cells (ML-1). By itself, TNF causes ML-1 to differentiate along the monocytic pathway. The cells exhibit an increase in Fc receptors and acquire the morphological characteristics of maturing phenotype. They remain viable and continue to proliferate (at greater than or equal to 50% of the control growth rate) even with 10(2)-10(4) units/ml TNF. IFN alone has similar effects, causing an increase in Fc receptors but little cytotoxicity. In contrast to either cytokine alone, the combination of TNF plus IFN causes a cessation of proliferation and extensive cell death. Cytotoxicity occurs in a synergistic fashion; it requires the simultaneous presence of both cytokines, occurring with concurrent but not sequential exposure. These different responses, differentiation (TNF alone) and cytotoxicity (TNF + IFN), occur with a similar range of doses (approximately 10(2)-10(4) units/ml) and in a similar time frame (beginning on day 2). In other cell types, IFN can augment either the differentiation-inducing or the cytotoxic effect of TNF. In ML-1, the combined application of TNF plus IFN results in a shift from differentiation to cytotoxicity.
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PMID:Differentiation-inducing and cytotoxic effects of tumor necrosis factor and interferon-gamma in myeloblastic ML-1 cells. 250 96

We have reported previously that the Kirsten murine sarcoma virus (Ki-MSV) that carries the v-Ki-ras oncogene prevents C3H10T 1/2 fibroblasts from being able to respond to interferon-gamma (IFN-gamma) with the expression of the class II major histocompatibility complex (MHC) antigen, H-2A. In this report we investigate further as to whether MSV or its parent virus Kirsten murine leukaemia virus (Ki-MLV) is able to reduce host class I MHC antigen expression. The results demonstrate that class I expression is diminished in MSV-infected cells over a time-course of 7 days after exposure to IFN-gamma and over a range of IFN-gamma concentrations. The optimal concentration of IFN-gamma for maximal class I expression remained unchanged. Cells infected with Ki-MLV, which failed to abolish the induction by IFN-gamma of class II antigens, also expressed lower levels of class I antigens, similar to those for cells infected with Ki-MSV, after exposure to IFN-gamma. It is likely therefore that the inhibition of class I induction is due to genetic material shared between the viruses, principally in the long terminal repeats (LTR), and hence that the mechanism of action is distinct from that responsible for the abolition of class II induction by Ki-MSV alone. Since class I antigens are required for CD8+ T cells (mainly cytotoxic T cells) to recognize (foreign) antigen this reduction in class I expression might lead to reduced visibility of infected cells to T cells and thus might contribute to the tumorigenicity of Ki-MSV-infected cells.
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PMID:Regulation of IFN-gamma-induced host cell MHC antigen expression by Kirsten MSV and MLV. I. Effects on class I antigen expression. 254 13

Cell lysates of the human monoblastic leukemia cell line, THP-1, have procoagulant activity (PCA) that is Ca++-dependent and not demonstrable in either Factor VII-, or Factor X-deficient plasma. The PCA of THP-1 cells was enhanced by human recombinant tumor necrosis factor-alpha (TNF-alpha) up to five fold. There was a dose-dependent increase in PCA when THP-1 cells were cultured with concentrations of TNF-alpha, up to 10 U/ml. PCA of cell lysates or whole cell preparations was measured in comparison to a rabbit brain thromboplastin standard. The effect of TNF-alpha was enhanced by recombinant human interferon-gamma (IFN-gamma). Cycloheximide inhibited the induction of PCA by THP-1 cells, which shows that the protein synthesis is essential to mediate the effect of TNF-alpha. THP-1 cells and U937 cells bound 125I-labeled TNF specifically. The numbers of receptors per cell were found to be 1,890 and 1,550 for THP-1 and U937 cells, respectively. Other lymphoid and myeloblastic leukemia cell lines examined did not have TNF receptors, indicating that the effect of TNF-alpha is mediated by the receptors on the cell surface.
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PMID:Induction of tissue factor-like activity of human monoblastic leukemia cell line by tumor necrosis factor-alpha. 255 90


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