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.