A NEW HUMAN CELL-LINE FOR THE MOLECULAR DISSECTION OF THE REQUIREMENT FOR INTERLEUKIN-1 IN THE PRODUCTION OF INTERLEUKIN-2 BY IMMATURE T-CELLS

An immature human T cell line, PER-117, can be induced to secrete interleukin-2 (IL-2). In contrast to mature T cells or the Jurkat cell line, PER-117 cells require interleukin-1 (IL-1) for optimal IL-2 secretion, in addition to calcium ionophore and phorbol 12-myristate 12-acetate (PMA). These requirements mirror the conditions reported to be optimal for normal immature T cell receptor (TCR) negative thymocytes. IL-1 did not substitute for either of the other signals required for IL-2 production, i.e., calcium ionophore or PMA, suggesting that IL-1 activates pathways different from those elicited by the two other stimuli. For optimal effect, IL-1 needed to be provided at the same time as the two other signals. Significantly, a signal provided by a low concentration of PMA (not leading to IL-2 induction by itself in the presence of calcium ionophore) was necessary. The studies reported here provide the first evidence that three signals are required for optimal IL-2 production in a human immature T cell line. PER-117 cells produce substantial levels of IL-2 and thus provide a model to study stage-specific signal transduction and transcriptional activation of the IL-2 gene in IL-1 responsive immature thymocytes.