REGULATION OF LYMPHOKINE EXPRESSION IN T-CELL ACTIVATION .1. RAPID LOSS OF INTERLEUKIN-SPECIFIC RNA AFTER REMOVAL OF THE STIMULATING SIGNAL

Resting T lymphocytes can be induced to express a variety of lymphokines after antigenic or mitogenic stimulation. Expression is regulated both at the transcriptional level, through induction of T cell-specific DNA-binding proteins, and at the post-transcriptional level through alteration of precursors or mRNA stability. To investigate whether lymphokine expression follows a preprogrammed course after activation of T cells or whether it is dependent on the continued monitoring of activating signals, we followed the fate of interleukin (IL)2, IL4 and IL2 receptor mRNA after removal of the stimulating signal concanavalin (Con A) by alpha-methylmannoside (alpha-MM). IL2 and IL4 needed continued stimulation of the cells for RNA expression, as shown by the rapid disappearance of IL2 and IL4 mRNA after addition of alpha-MM to stimulated cells, while IL2 receptor mRNA which is also induced after Con A stimulation was minimally influenced. In the case of both IL no new mature mRNA was generated after removal of the stimulating signal. The T1/2 of IL2 mRNA remained unchanged after alpha-MM treatment as compared to actinomycin D treatment, while IL4 mRNA became labilized after withdrawal of the signal.