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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene formed syncytia by cocultivation with Friend murine leukemia virus (MuLV)-producing cells. On the other hand, parental 3Y1 cells and those derivatives induced by other tumor viruses or chemical carcinogen showed no MuLV-mediated syncytium formation [N. Momozaki et al. (1990) Arch. Virol. 115: 123-126]. The expression of major histocompatibility complex (MHC) class I mRNA and antigens was significantly reduced in these Ad12- and E1A-transformed 3Y1 cells. In contrast, other tumor virus-and chemical carcinogen-transformed 3Y1 cells expressed MHC class I almost in normal levels as did parental 3Y1 cells. Furthermore, Ad12-transformed 3Y1 cells which started to express the transfected exogenous MHC class I gene, H-2Ld, showed no more MuLV-mediated 3Y1 cell fusion. These results indicate that the expression of MHC class I on the cell membrane is closely related to the inhibition of 3Y1 cell fusion by MuLV.
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PMID:Suppression of murine leukemia virus-mediated 3Y1 cell fusion by expression of mouse MHC class I. 186 24

The mechanisms whereby RNA leukemia viruses cause T lymphocyte leukemias or lymphomas after a long latent period are not understood. We report here that infection of human T lymphocyte lines with a murine leukemia virus results in up-regulation of a number of lymphocyte-specific cell surface Ag. These proteins include CD2, CD3, CD4, the TCR, and MHC class I Ag. The expression of other cell surface proteins, such as LFA-3, are unaffected by the presence of the retrovirus. This up-regulation occurs at the level of the mRNA transcripts encoding these proteins, and is the result of increased transcription of the respective genes. The increases in transcription are the result of a trans-activation process by the leukemia virus. The transient introduction of chimeric genes consisting of MHC class I gene promoter sequences attached to the reporter gene CAT into human T cells containing murine retrovirus produces stimulated transcription of the reporter gene. Subgenomic portions of the murine leukemia virus containing the long terminal repeats and the 5' untranslated region are sufficient to produce transactivation of the same set of T cell genes as the whole leukemia virus. The finding that murine leukemia viruses enhance transcription and expression of a group of T cell surface proteins, all of which have been reported to be capable of transducing an activating signal to the lymphocyte, may be relevant to the pathophysiologic mechanisms whereby these viruses induce leukemias and lymphomas.
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PMID:trans-Activation of genes encoding activation-associated human T lymphocyte surface proteins by murine retroviral sequences. 200 5

Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.
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PMID:Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia. 207 89

To study the regulation of MHC class I gene expression during embryonic development, we have characterized a number of clonal cell lines derived from somite stage mouse embryos that were established with or without infection by several transforming retroviruses in combination with murine leukemia viruses. Unlike embryonal carcinoma (EC) cells that have been used as a model for early embryos, the cell lines derived from somite stage embryos are negative for stage specific embryonic Ag-1 and do not appear to differentiate after retinoic acid treatment. Morphology varies from clone to clone and is distinct from that of F9 and other EC cells. In agreement with previous findings in in vivo embryos, expression of surface MHC class I antigen in 57 new clones is either undetectable or low (with variability). All of the clones respond to the addition of interferons and express MHC class I antigens at high levels, but the kinetics of mRNA accumulation vary considerably. To examine the basis of the generally low or absent MHC class I gene expression in these cells, we tested promoter activity of a MHC class I gene by CAT assay after transient DNA transfection. Regardless of the basal levels of mRNA or surface Ag, CAT activity directed by various portions of the 5' flanking region of the MHC class I gene was uniformly low. The cells showed neither the negative nor the positive regulation of MHC class I genes that had been noted respectively for EC cells and for cells expressing the Ag constitutively. The pattern seen in the new cell lines suggests that there is an intermediate stage in the developmental regulation of MHC class I gene expression that may operate during the middle to late stage of fetal development.
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PMID:Establishment of cell lines from somite stage mouse embryos and expression of major histocompatibility class I genes in these cells. 245 81

T lymphoma induction by the mink cell focus-inducing murine leukemia virus MCF 1233 in C57BL/10 and C57BL/6 mice is influenced by a strongly Th-dependent, H-2I-A-restricted antiviral immune response (25). We compared the MHC class I as well as viral env and gag antigenic cell surface profiles of frequent T lymphomas of H-2I-A nonresponder-type mice to that of rare T lymphomas of H-2I-A responder-type mice. Membrane immunofluorescence studies, with a panel of anti-env mAbs (reactive with the highly conserved gp70f epitope, the p15Ec epitope, and the gp70-p15E complex), a polyclonal anti-p30 serum, and anti-H-2 class I mAbs, showed that all 17 nonresponder tumors tested expressed high levels of both env and gag viral proteins, and 15 of these 17 nonresponder tumors expressed high levels of H-2 class I K and D antigens. In contrast, 10 of 11 responder lymphomas lacked env and/or gag determinants. The only responder lymphoma with both strong env and gag expression failed to express H-2K and -D antigens. Preferential loss of env or gag expression did not correlate with H-2 class I allelic specificities. Both responder and nonresponder T lymphoma DNA contained multiple, predominantly MCF-like, newly acquired proviral integrations. Differences in viral antigen cell surface expression were confirmed at cytoplasmic and RNA levels. The amounts of 8.2- and 3.2-kb viral RNA were greatly reduced in two responder lymphomas when compared with four nonresponder lymphomas. In both responder lymphomas, aberrantly sized viral RNA species were found. Upon in vivo passage of these responder lymphomas in either immunocompetent or T cell-deficient nu/nu mice, it was found that various molecular mechanisms may underlie the lack of viral antigen expression at the cell surface of these lymphomas. One lymphoma re-expressed viral antigens when transplanted with nu/nu mice, whereas the other remained stably gag negative. The combined findings indicate that an H-2I-A-regulated antiviral immune response not only strongly reduces T lymphoma incidence, but also forces T lymphomas that still arise to poorly express viral antigens, thus explaining their escape from immunosurveillance.
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PMID:Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens. 253 50

C57BL/6 (B6, H-2b) mice are CTL responders to both Sendai virus and Moloney leukemia virus. In the former response the H-2Kb class I MHC molecule is used as CTL restriction element, in the latter response the H-2Db molecule. B6 dendritic cells (DC) are superior in the presentation of Sendai virus Ag to CTL in comparison with B6 normal spleen cells. Con A blasts have even less capacity to present viral Ag than NSC, and LPS blasts show an intermediate capacity to present viral Ag. H-2Kb mutant bm1 mice do not generate a CTL response to Sendai virus, but respond to Moloney leukemia virus, as demonstrated by undetectable CTL precursors to Sendai virus and a normal CTL precursor frequency to Moloney virus. Compared to B6 mice, other H-2Kb mutant mice show decreased Sendai virus-specific CTL precursor frequencies in a hierarchy reflecting the response in bulk culture. The Sendai virus-specific CTL response defect of bm1 mice was not restored by highly potent Sendai virus-infected DC as APC for in vivo priming and/or in vitro restimulation. In mirror image to H-2Kb mutant bm1 mice, H-2Db mutant bm14 mice do not generate a CTL response to Moloney virus, but respond normally to Sendai virus. This specific CTL response defect was restored by syngeneic Moloney virus-infected DC for in vitro restimulation. This response was Kb restricted indicating that the Dbm14 molecule remained largely defective and that a dormant Kb repertoire was aroused after optimal Ag presentation by DC. In conclusion, DC very effectively present viral Ag to CTL. However, their capacity to restore MHC class I determined specific CTL response defects probably requires at least some ability of a particular MHC class I/virus combination to associate and thus form an immunogenic complex.
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PMID:Failure or success in the restoration of virus-specific cytotoxic T lymphocyte response defects by dendritic cells. 283 54

Cells from the peripheral blood of B-cell chronic lymphocytic leukaemia (CLL) patients were examined serologically for the expression of cell surface MHC class II antigens with monoclonal antibodies (mAbs) specific for the products of HLA-DP, -DQ and -DR genes, and mRNAs from the cells of three patients were analysed with a cDNA probe specific for DR beta chain genes. In 12 cases of CLL studied by indirect immunofluorescence and FACS analysis, a variable proportion of cells failed to express detectable levels of HLA-DP and HLA-DQ antigens at the cell surface, although greater than 90% of the cells had detectable expression of HLA-DR antigens. In all cases, greater than 90% of the cells expressed MHC class I antigens and the majority of cells reacted with the Leu-1 (CD5) mAb. Cells from different patients expressed variable levels of MHC class II antigens, and this was reflected in the finding of variable levels of mRNA detectable with the cDNA probe. Culture of cells with the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced much increased levels of expression of MHC class II antigens. HLA-DP and -DQ antigens were expressed on greater than 90% of the cells in all cases studied after culture of the cells with TPA, and MHC class II specific mRNA transcripts were correspondingly increased. In a single case of plasma cell leukaemia studied, MHC class II antigens were not detectable at the cell surface and their expression was not induced after culture of the cells with TPA.
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PMID:Expression of MHC class II antigens in human B-cell leukaemia, and increased levels of class II antigens and DR-specific mRNA after stimulation with 12-O-tetradecanoyl phorbol-13-acetate. 351 24

Major histocompatibility complex (MHC) class I molecules can function as specific target antigens in T-cell-mediated cytotoxity. In addition, T cells can kill target cells through non-MHC antigens, for example, virally infected cells, if the target and effector cells express the same MHC class I antigens. Consequently, quantitative and/or qualitative variations in the expression of the H-2/HLA antigens on the target cells could interfere with MHC-restricted immune reactions. We have reported that the AKR leukaemia cell line K36.16, a subline of K36 (ref. 3), on which the H-2Kk antigen cannot be detected, is resistant to T-cell lysis and grows very easily in AKR mice. Other AKR tumour cell lines, like 369, which have a relatively large amount of H-2Kk on their surface, are easily killed by T cells in vitro and require a much larger inoculum to grow in vivo. Monoclonal antibodies against H-2Kk, but not against H-2Dk, prevented the killing by T cells. This suggests that some tumour cells grow in vivo because tumour-associated antigen(s) cannot be recognized efficiently by the host's immune system, due to the absence of MHC molecules which would function as restriction elements for T-cell cytotoxicity. We have tested this hypothesis by introducing the H-2Kk gene into the H-2Kk-deficient AKR tumour cell line K36.16 and have now demonstrated directly the biological relevance of H-2Kk antigen expression in the regulation of the in vivo growth of this tumour cell line.
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PMID:Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. 633 39

Tumor cell variants were derived from the BW5147 T-cell lymphoma that differ in major histocompatibility complex (MHC) class I antigen expression, tumorigenicity and metastatic potential. In general, increased H-2Kk expression was found to be correlated with a reduced tumorigenicity and spontaneous metastasis. CD8+ T cells were identified in the immune recognition of such variants, implicating a role for H-2Kk in the presentation of tumor-associated antigens. In the present study, H-2Kk+ BW variants were transfected with a gene encoding interferon-gamma (IFN-gamma), a potent inducer of MHC class I expression. The resulting transfectants exhibited an increased expression of H-2Kk and concomitantly an inability to generate visible tumors and a reduced metastatic capacity. Furthermore, immunization with the IFN-gamma transfectants resulted in an increased generation of cytotoxic T lymphocytes (CTLs) that lysed both the transfectants and the parental tumor cells. Based on these results, vaccinations with the IFN-gamma transfectants were performed against the parental tumor cells. The results clearly demonstrated that such vaccinations reduced significantly the tumorigenicity and metastatic capacity of the parental tumor cells. Hence, in this tumor model, IFN-gamma gene transfection provides a means to immunogenize H-2Kk+ BW tumor cells.
Leukemia 1995 Oct
PMID:Immunogenization of a murine T-cell lymphoma via transfection with interferon-gamma. 747 4

The transcriptional activation of the major histocompatibility complex (MHC) class I genes by both type I (alpha/beta) and II (gamma) interferons (IFNs) has been extensively studied, and it has been shown that the upregulation of several DNA-binding proteins is critical for this process. In our laboratory, we introduced the mouse H-2Kb gene into the AKR mouse leukaemia cell line K36.16 to effect the generation of tumor-specific immunity. Individual clones were selected and studied. Whereas the MHC class I genes in most of the clones obtained could be stimulated by interferons, one of the clones obtained, clone Kb-S27, failed to be induced, or was at best poorly induced by IFN-alpha/beta and -gamma. Both the exogenous H-2Kb and the endogenous H-2Dk genes behaved in the same manner and were not stimulated by IFNs. The lack of response to IFNs by clone Kb-S27 also resulted in its resistance to the antiproliferative effects of IFNs. This lack of IFN-induction by clone Kb-S27 was not simply due to a change in its surface interferon receptors. Gel-retardation assay and northern blot analysis both demonstrated the lack of induction of the IRF-1 DNA-binding factor in clone Kb-S27. In addition, northern blot analysis showed that the IRF-2 gene expression in clone Kb-S27 was upregulated when compared with the other IFN-inducible clones.
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PMID:Characterization of a novel IRF-1-deficient mutant cell line. 750 33


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