Quantitative and qualitative differences in IL-2 and IL-4 expression in primary and secondary T cell stimulation.
Lymphocytes were concanavalin A (Con A) primed and the signal was withdrawn 4-48 h post-stimulation by alpha-methyl-D-mannopyranoside (alpha MM) treatment. Upon restimulation IL-2 and IL-4 RNA expression was found to be greatly enhanced. Re-expression of lymphokine RNA was dependent on signals delivered by Con A, anti-CD3 antibodies or phorbolester plus ionomycin, and could not be achieved by either IL-2, phorbolester or ionomycin alone. Increased IL-2 re-expression was only possible when alpha MM was added early after primary stimulation, while the ability for enhanced IL-4 RNA re-expression persisted. IL-2 and IL-4 RNA re-expression was characterized by increases in steady state precursor RNA levels and thus, presumably, increased rates of transcription. However, the high accumulation of IL-2 RNA observed upon restimulation was also due to greatly increased RNA stability (greater than 4 h versus 30 min after primary stimulation). Thus, secondary expression of IL-4 RNA is persistent and mostly due to quantitative changes in transcription, whereas enhanced re-expression of IL-2 RNA also results from altered post-transcriptional regulation. This phenotype, however, is only short lived.
Bommhardt
U
U
Institute of Virology and Immunobiology, Würzburg, Germany.
Sadlack
B
B
Schimpl
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation; D007376:Interleukin-2 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008766:Methylmannosides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D008766:Methylmannosides; D015847:Interleukin-4; C008466:methylmannoside; D012313:RNA; D016572:Cyclosporine; D003513:Cycloheximide; D011493:Protein Kinase C; D002118:Calcium