A highly leukemogenic radiation leukemia virus isolate is a thymotropic, immunosuppressive retrovirus with a unique rna structure

David, Ya'acob Ben; Kotler, Moshe; Yefenof, Eitan

doi:10.1002/ijc.2910390415

Cited by 7 publications

(3 citation statements)

References 29 publications

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“…Experiments reported by Haran-Ghera et al (6) demonstrated that cells with PL characteristics appear in the thymus approximately 2 weeks after inoculation with Rad-LV. The PL cells constitute 1-3% of the total thymic lymphocyte population (5). These cells persist for several months, after which time, a clonal lymphoma emerges.…”

Section: Discussionmentioning

confidence: 99%

“…Shortly after inoculation with the virus, a pleioclonal population of preleukemic (PL) cells, representing 1-3% of the total population (5), is detected in the thymus (6)(7)(8). The PL cells are not malignant but can progress to lymphoma when inoculated intrathymically into syngeneic recipients (9,10).…”

mentioning

confidence: 99%

“…As a result, an autocrine loop is established, enabling both the proliferation and maintenance of virus-infected PL cells. Progression of the PL cells to overt lymphoma involves the selective growth ofa single PL cell clone that has acquired a fully malignant phenotype (5,10).…”

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confidence: 99%

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Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.

Yefenof

Abboud

Epszteyn

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Radiation leukemia virus (RadLV)-induced preleukemic (PL) latency is characterized by the appearance of virus-infected PL cells in the thymus. The survival of these PL cells is dependent upon autostimulation with interleukin 4 (IL-4). We have intervened prophylactically in RadLV-induced preleukemia by using cyclosporin-A (CSA), which inhibits IL-4 production, and an immunotoxin (ITx) that kills PL cells. CSA efficiently inhibited IL-4 secretion from RadLV-induced PL and leukemic cells, and its administration to PL mice caused a significant delay in their death. An ITx consisting of antiRadLV glycoprotein-70 (gp70) antibody coupled to ricin A chain efficiently inhibited protein synthesis in virus-infected cells in vitro and, when in'ected into PL mice, also delayed their death. Combined treatment with CSA and ITx prevented 75% of the treated PL mice from developing lymphoma. These results show that the development of malignancy from a premalignant state can be averted by a combination of therapeutic modalities that decrease the size and growth rate of the premalignant cell population.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.

Yefenof

Abboud

Epszteyn

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Induction of IL‐4 secretion by the radiation leukemia virus (RadLV): Role in autocrine growth stimulation of RadLV infected pre‐leukemic cells

Yefenof

Ela

Kotler

et al. 1992

Intl Journal of Cancer

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Intrathymic inoculation of radiation-leukemia virus (RadLV) into C57BL/6 mice induces a population of pre-leukemic (PL) T cells which progress into clonal, mature thymic lymphomas after a latency period of 3 to 5 months. In order to understand how PL cells are retained in the thymus for a prolonged period of time we determined whether RadLV infected cells secrete and/or respond to a T-cell growth factor that may be involved in the long-term maintenance of a thymic PL-cell pool. We have previously found that in vitro proliferation of RadLV-infected PL cells is IL-4-dependent. Here we show that RadLV induces IL-4 secretion and IL-4 receptor (IL-4R) expression in normal thymic lymphocytes. RadLV-infected PL thymocytes express IL-4R and secrete IL-4. Their IL-4 secretion could be enhanced if incubated in the presence of RadLV and this enhancement was inhibited by anti-RadLV antibodies. Several RadLV-induced lymphoma lines secreted IL-4 and/or expressed IL-4R, but these features were not essential for their continuous growth. The results suggest that RadLV induces IL-4-dependent autocrine growth which maintains a population of PL T cells in the thymus. Transition from a PL state to overt thymic lymphoma involves emancipation of a PL cell from IL-4 dependency.

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Characterization of mature and immature Rad LV‐Induced thymic T‐cell lines for tumorigenesis and mhc‐class‐I gene expression

Bashi

Ehrlich

1995

Intl Journal of Cancer

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Class-I-MHC molecules are divided into class-Ia molecules, which play major roles in recognition of virus-infected cells, graft rejection and immune responses against tumors, and class-Ib molecules, which are less polymorphic and may be responsible for presenting unique classes of peptides. Our report characterizes RadLV-induced thymic T-cell lines that differ both in their tumorigenic potential and in the level of protein for class-Ia and TL genes. The PD1.1 cell line is CD4-CD8+ and expresses relatively high levels of class-I as compared with the CD4+CD8+ PD1.2 cell line. These class-I-expression levels correlate with thymocytes and splenic T cells of the same phenotype, except that normal cells fail to express TL3b. Interferon-treated PD1.2 cells demonstrate significantly lower levels of class-I expression than do interferon-treated PD1.1 cells, and were shown to contain large amounts of degraded class-I mRNA, at least some of which was TL in origin. These RNA products were not detected in PD1.1 cells, suggesting the existence of a mechanism controlling cell-specific and gene-specific mRNA stability. Such RadLV-induced cell lines provide a means for obtaining stage-specific T cells, which can be used for studying the regulation of class-I gene expression during T-cell differentiation, as well as factors that differentially regulate class-Ia and class-Ib expression and are potentially useful for studying T-cell differentiation in general.

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A highly leukemogenic radiation leukemia virus isolate is a thymotropic, immunosuppressive retrovirus with a unique rna structure

Cited by 7 publications

References 29 publications

Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.

Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin.

Induction of IL‐4 secretion by the radiation leukemia virus (RadLV): Role in autocrine growth stimulation of RadLV infected pre‐leukemic cells

Characterization of mature and immature Rad LV‐Induced thymic T‐cell lines for tumorigenesis and mhc‐class‐I gene expression

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