Regulation of lymphokine expression in T cell activation. I. 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, IL 4 and IL 2 receptor mRNA after removal of the stimulating signal concanavalin (Con A) by alpha-methylmannoside (alpha MM). IL 2 and IL 4 needed continued stimulation of the cells for RNA expression, as shown by the rapid disappearance of IL 2 and IL 4 mRNA after addition of alpha MM to stimulated cells, while IL 2 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 IL 2 mRNA remained unchanged after alpha MM treatment as compared to actinomycin D treatment, while IL 4 mRNA became labilized after withdrawal of the signal.