RETROVIRAL INTERLEUKIN-5 GENE-TRANSFER INTO INTERLEUKIN-5-DEPENDENT GROWING CELL-LINES RESULTS IN AUTOCRINE GROWTH AND TUMORIGENICITY

Two interleukin 5 (IL 5)-specific retroviral expression vectors have been constructed containing the neomycin gene as selectable marker and either the mouse IL 5 cDNA region or the rat genomic IL 5 gene under the control of the thymidine kinase promoter. High viral titer supernatants derived from the transfected or infected packaging cell line psi-2 were used to infect the two cell lines B13 and T88M whose growth is dependent on exogenous IL 5. Infection resulted in G418 resistance and IL 5-independent growth with a high frequency. Clones were established which secrete between 2 and > 1000 U IL 5. The proliferation of the IL 5 autocrine growing cells could be inhibited by an antibody directed against the IL 5 receptor indicating that they grow as a result of the endogenously produced IL 5. Regardless of the amount of IL 5 they produced, all of the clones were highly tumorigenic in nucle mice. The phenotype of the tumors was indistinguishable from that of the injected cells. T88M or B13 cells infected with a control virus neither produced IL 5, nor became factor independent, nor produced tumors. Together, the IL 5 gene transfer and expression into IL 5-dependent growing cells are in accordance with the "autocrine growth" hypothesis and contrast analogous experiments with IL 4.