Induction of IL-4 secretion by the radiation leukemia virus (RadLV): role in autocrine growth stimulation of RadLV infected pre-leukemic cells.
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.
Yefenof
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E
Lautenberg Center for General & Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Ela
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C
Kotler
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M
Vitetta
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ES
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D008223:Lymphoma / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D011289:Preleukemia / Q000503:physiopathology*; D016721:Radiation Leukemia Virus / Q000472:pathogenicity*; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000473:pathology
D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D004247:DNA