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.
Swoboda
R
R
Institute of Virology and Immunobiology, University of Würzburg, FRG.
Bommhardt
U
U
Schimpl
A
A
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008213:Lymphocyte Activation; D008766:Methylmannosides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D007376:Interleukin-2; D008766:Methylmannosides; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D003609:Dactinomycin; D015847:Interleukin-4; C008466:methylmannoside