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   <subfield code="a">Autonomous growth of lymphoid cells following IL-2 expression from retrovirus vectors containing HIV-1 trans -acting elements</subfield>
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   <subfield code="c">[Ilya Shapiro, Craig Meier, Victoria Vlach, Thomas McDonald, Hans Wigzell, Mario Stevenson]</subfield>
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   <subfield code="a">The human immunodeficiency virus type I (HIV-1) possesses powerful regulatory elements that control the rate of replication of HIV-1 and subsequent processing ofHIV-1 genes. We have used this regulatory mechanism to drive expression of foreign genes inserted in retrovirus vectors. This approach was used to express the humanIL-2 gene in IL-2-dependent mouse CTLL-2 cells to determine the role of autonomous growth in maintaining proliferation of virus-infected T lymphocytes during HTLV-1-induced adult T-cell leukemia (ATL). Expression of IL-2 sequences in IL-2-dependent mouse CTLL-2 cells resulted in autonomous growth of IL-2-independent CTLL-2 clones. Endogenous expression of IL-2 appeared to interrupt normal constraints of growth in that these IL-2-independent clones showed reduced cell-density-dependent inhibition but not a tumorigenic phenotype. IL-2-independent CTLL-2 clones did not secrete detectable quantities of IL-2 into culture supernatant and exhibited reduced sensitivity to the inhibitory effects of both IL-2 and IL-2 receptor antibody. These results suggest that the IL-2 autocrine loop within these cells involves intracellular IL-2/IL-2 receptor binding. The apparent lack of IL-2 production and poor responsiveness to IL-2 or IL-2 antibodies displayed by cell lines from ATL patients may be explained by an intracellular IL-2/IL-2 receptor autocrine loop.</subfield>
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